MPAL and Acute leukaemia types: Difference between pages
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<span style="color:navy">'''SECTION 1: Establishing the primitive nature of the blast cells in AML'''</span> | |||
''The recognition of blast cells requires them to have features of primitive phenotype, markers can help support this, although morphology may also be required'' | |||
The expression of some markers is typically associated with primitive cells and can help recognise the primitive nature of blast cells. These markers may also have some lineage specificity. | |||
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<span id="anchor_0"></span>. | <span id="anchor_0"></span>. | ||
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!colspan="2" <span style="font-size:90%; font-color:navy; text-align:center; border: 1px solid black; background:pale gray">|'''MARKERS USEFUL TO CONFIRM PRIMITIVE NATURE OF BLAST CELLS IN AML'''</br></span> | |||
|- | |||
|colspan="2" style = "font-size:90%; color:black; background:#ddeee1" |These markers are useful to recognise the primitive nature of cells rather than specific lineage | |||
<span style="font-size:80%;></br>The first step in AML diagnosis to establish the primitive nature of the abnormal cells:</br> | |||
<span style="font-size:80%;>'''(1)''' Typically AML blasts have low CD45 expression and cause low side scatter. This means that they form a relatively uniform and distinctive population that is clearly separate from that of lymphocytes on CD45/SSc plots ([[CD45|for further details see this section]]). It is important to realise however also not all AML cases will fit this pattern of low-CD45/low-SSc - particularly [[APL]] and [[monocytic AML]].</br></span> | |||
<span style="font-size:80%;>'''(2)''' Additional markers that are often expressed on myeloid cells can help confirm the primitive nature of the cells: in AML this is most often CD34, although other markers may contribute.</br> | |||
</span> | |||
</div></div></div> | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD45]]''' | |||
|colspan="1" style = "font-size:84%;"|A marker expressed by all leukocytes and their precursors. In AML expression is characteristically "weak" i.e. significantly less intense than normal lymphocytes or monocytes. In monocytic AML expression may be stronger. | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD34]]''' | |||
|colspan="1" style = "font-size:84%;"|Frequently expressed by AML blast cells (40-80% of cases) - most often in less differentiated forms of AML. Expression is also seen frequently (and often more strongly) in ALL''' | |||
|- | |||
|colspan="2" style = "font-size:90%; color:black; background:#eedddd" |Other markers that may be associated with primitive nature in AML | |||
|- | |||
|colspan="2" style = "font-size:90%;|In the context of a proven AML diagnosis a number of markers may be expressed that are considered to predominantly reflect the primitive nature of the cells. Some of these are more frequently associated with lymphoid disorders, but providing other criteria for AML are met they should simply be considered to show "primitivity". These include: [[CD38]], [[HLA-DR]], [[TDT]], [[CD7]]. | |||
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|} | |||
</div> | |||
---- | |||
---- | |||
<span style="color:navy">'''SECTION 2: Assigning blast cells as myeloid lineage'''</span> | |||
''Essentially, leukaemic cells can be assigned solely to myeloid lineage under one of two circumstances:'' | |||
'''1:''' A '''myeloid lineage-defining''' marker is expressed '''and''' no B or T-lineage defining markers are expressed | |||
<span id="anchor_1"></span>. | |||
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!colspan="2" <span style="font-size:90%; colour:white; text-align:center; border: 1px solid black; background:pale gray">|'''MYELOID-LINEAGE-DEFINING MARKERS'''</span><span style="font-size:90%; text-align:left; background:white"> | |||
|- | |||
|colspan="2" style = "font-size:90%; color:black; background:#ddeee1" |The present WHO classification recognises only one marker as lineage-defining in AML | |||
<div class="mw-collapsible mw-collapsed" data-expandtext="Click for explanation" data-collapsetext="Hide explanation"> | |||
<div class="mw-collapsible-content"> | |||
<span style="font-size:90%;></br>Expression of MPO is lineage defining and should indicate AML (or [[MPAL]] if lymphoid lineage also confirmed) | |||
</br> | |||
</span> | |||
</div></div></div> | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[MPO]]''' | |||
|colspan="1" style = "font-size:84%;"|A '''lineage-defining''' marker in AML when expressed (around 80% of cases). More frequent in cases with granulocytic maturation. When detected by flow cytometry is diagnostic of myeloid differentiation is established (either AML or MPAL) | |||
|} | |||
</div> | |||
'''2:''' At least two '''myeloid-associated markers''' are expressed, '''and''' lineage cannot be assigned as B cell or T cell by lineage-specific or lineage-associated lymphoid markers | |||
<span id="anchor_1"></span>. | |||
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!colspan="2" <span style="font-size:90%; colour:white; text-align:center; border: 1px solid black; background:pale gray">|'''MYELOID-LINEAGE ASSOCIATED MARKERS (general)'''</span><span style="font-size:90%; text-align:left; background:white"> | |||
|- | |||
|colspan="2" style = "font-size:90%; color:black; background:#ddeee1" |Each of these markers is frequently expressed in AML (80% of cases). They support a diagnosis of myeloid lineage, but are not sufficiently specific to be AML-defining when expressed alone | |||
<div class="mw-collapsible mw-collapsed" data-expandtext="Click for explanation" data-collapsetext="Hide explanation"> | |||
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<span style="font-size:90%;></br>These markers may be considered the most frequent markers expressed by AML. Having said that each may also be expressed by cells of ALL. General concepts: | |||
* In the absence of markers suggesting alternative lineage expression of two of these markers may be used to support a diagnosis of AML | |||
* One or more of CD117, CD33, CD13 may be expressed by otherwise typical ALL is allowed and does not change lineage assignment | |||
</br> | |||
</span> | |||
</div></div></div> | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD117]]''' | |||
|colspan="1" style = "font-size:84%;"|An early marker of myeloid lineage, seen in up to 80% of AML and vauable in recognising more primitive differentaiion forms (note that aberrant expression is seen in up to 20% of ALL cases) | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD33]]''' | |||
|colspan="1" style = "font-size:84%;"|A good marker for AML, particularly for those cases with granulocytic maturation, CD33 is often less strongly expressed in AML with monocytic dfferentiation and strongly expressed in APL. | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD13]]''' | |||
|colspan="1" style = "font-size:84%;"|A good lineage marker for AML that is acquired a little later in differentation than CD117 or CD33; expression of CD13 is often higher than CD33 in AML with monocytic differentiation. | |||
|- | |||
|} | |||
</div> | |||
The markers already decribed are sufficient to make a diagnosis of typical AML in most cases. Typically the markers in this table are associated with specific features of differentiation so will not be present in all cases, but may be helpful as "lineage-assocated" markers in difficult cases. Care should be taken when doing so, since in some cases specificity may be lower than for typical myeloid markers. | |||
<span id="anchor_1"></span>. | |||
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{| class="wikitable" style="color:black; background-color:#ffffff;" cellpadding="0" | |||
!colspan="2" <span style="font-size:90%; colour:white; text-align:center; border: 1px solid black; background:pale gray">|'''MYELOID LINEAGE MARKER ASSOCIATED WITH SPECIFIC DIFFERENTIATION'''</span><span style="font-size:90%; text-align:left; background:white"> | |||
|- | |||
!colspan="2" style = "font-size:90%; background:#ddeee1"|While most cases of AML will be diagnosed using MPO, CD117, CD13 and CD33, some cases may be more difficult, particularly those significant differentation. In those cases supplementary antibodies may be helpful to make a diagnosis or confirm a pattern of differentation. | |||
<div class="mw-collapsible mw-collapsed" data-expandtext="Click for explanation" data-collapsetext="Hide explanation"> | |||
<div class="mw-collapsible-content"> | |||
<span style="font-size:90%;></br>Some additional markers are regarded as indicating primitive nature when expressed by AML blasts; these markers may be more usually assocated with T-lineage or B-lineage ALL, but when expressed in AML they are considered to indicate less differentiated forms.</br> | |||
</span> | |||
</div></div></div> | |||
|- | |||
!colspan="2" style = "font-size:90%;background:white;"|Granulocytic lineage markers | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD10]]''' | |||
|colspan="1" style = "font-size:84%;"|Most frequently a marker expressed in ALL subtypes, but expression of CD10 may occur some more differentiated cases of AML (particularly APL and AML with monocytic maturation | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD11b]]''' | |||
|colspan="1" style = "font-size:84%;"|One of tne of the first lineage-markers acquired in AML with good relative specificity | |||
|- | |||
!colspan="2" style = "font-size:90%;background:white;"|Monocytic lineage markers | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD11c]]''' | |||
|colspan="1" style = "font-size:84%;"|One of tne of the first lineage-markers acquired in AML with good relative specificity | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD14]]''' | |||
|colspan="1" style = "font-size:84%;"|A good marker for AML that is often less strongly expressed in monocytic forms | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD64]]''' | |||
|colspan="1" style = "font-size:84%;"|A good lineage marker for AML aquired a little later, higher than CD13 in monocytic forms | |||
|- | |||
!colspan="2" style = "font-size:90%;background:white;"|'''Features associated with erythroid differentiation''' | |||
|- | |||
|colspan="2" style = "font-size:90%;background:white;"|Most often [[CD34]], [[CD45]] and [[HLA-DR]] are weak or negative, although [[CD117]] and [[CD36]] are generally expressed. There may be some expression of platelet markers in some cases. | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD71]]''' | |||
|colspan="1" style = "font-size:84%;"|Frequently expressed though not fully lineage specific | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD235]]''' | |||
|colspan="1" style = "font-size:84%;"|A good marker of erythroid differentiation but acquired late and therefore may not be expressed | |||
|- | |||
!colspan="2" style = "font-size:90%;background:white;"|'''Features associated with megakaryocytic differentiation''' | |||
|- | |||
|colspan="2" style = "font-size:90%;background:white;"|Most often [[CD34]], [[CD45]] and [[HLA-DR]] are weak or negative, although [[CD13]] and [[CD33]] may be expressed | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD41]]''' | |||
|colspan="1" style = "font-size:84%;"|Platelet glycoprotein IIbIIIa | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD61]]''' | |||
|colspan="1" style = "font-size:84%;"|Platelet glycoprotein IIIa | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD42b]]''' | |||
|colspan="1" style = "font-size:84%;"|Platelet gycoprotein Ib | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD36]]''' | |||
|colspan="1" style = "font-size:84%;"|Relatively non-specific (seen in erythroid and monocytic leukaemias) but often strongly expressed | |||
</span> | |||
|} | |||
</div> | |||
<span id="anchor_1"></span>. | |||
<div style="width: 100%; border: 1px solid black; font-size:100%"> | |||
{| class="wikitable" style="color:black; background-color:#ffffff;" cellpadding="0" | |||
!colspan="2" <span style="font-size:90%; colour:white; text-align:center; border: 1px solid black; background:pale gray">|'''OTHER MARKERS OF MYELOID LINEAGE'''</span><span style="font-size:90%; text-align:left; background:white"> | |||
|- | |||
!colspan="2" style = "font-size:90%; background:#ddeee1"|While most cases of AML will be diagnosed using MPO, CD117, CD13 and CD33, some cases may be more difficult, particularly those significant differentation. In those cases supplementary antibodies may be helpful to make a diagnosis or confirm a pattern of differentation. | |||
<div class="mw-collapsible mw-collapsed" data-expandtext="Click for explanation" data-collapsetext="Hide explanation"> | |||
<div class="mw-collapsible-content"> | |||
<span style="font-size:90%;></br>Some additional markers are regarded as indicating primitive nature when expressed by AML blasts; these markers may be more usually assocated with T-lineage or B-lineage ALL, but when expressed in AML they are considered to indicate less differentiated forms.</br> | |||
</span> | |||
</div></div></div> | |||
|- | |||
!colspan="2" style = "font-size:90%;background:white;"|Granulocytic lineage markers | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD10]]''' | |||
|colspan="1" style = "font-size:84%;"|One of tne of the first lineage-markers acquired in AML with good relative specificity | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD11b]]''' | |||
|colspan="1" style = "font-size:84%;"|One of tne of the first lineage-markers acquired in AML with good relative specificity | |||
|- | |||
!colspan="2" style = "font-size:90%;background:white;"|Monocytic lineage markers | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD11c]]''' | |||
|colspan="1" style = "font-size:84%;"|One of tne of the first lineage-markers acquired in AML with good relative specificity | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD14]]''' | |||
|colspan="1" style = "font-size:84%;"|A good marker for AML that is often less strongly expressed in monocytic forms | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD64]]''' | |||
|colspan="1" style = "font-size:84%;"|A good lineage marker for AML aquired a little later, higher than CD13 in monocytic forms | |||
|- | |||
!colspan="2" style = "font-size:90%;background:white;"|'''Features associated with erythroid differentiation''' | |||
|- | |||
|colspan="2" style = "font-size:90%;background:white;"|Most often [[CD34]], [[CD45]] and [[HLA-DR]] are weak or negative, although [[CD117]] and [[CD36]] are generally expressed. There may be some expression of platelet markers in some cases. | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD71]]''' | |||
|colspan="1" style = "font-size:84%;"|Frequently expressed though not fully lineage specific | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD235]]''' | |||
|colspan="1" style = "font-size:84%;"|A good marker of erythroid differentiation but acquired late and therefore may not be expressed | |||
|- | |||
!colspan="2" style = "font-size:90%;background:white;"|'''Features associated with megakaryocytic differentiation''' | |||
|- | |||
|colspan="2" style = "font-size:90%;background:white;"|Most often [[CD34]], [[CD45]] and [[HLA-DR]] are weak or negative, although [[CD13]] and [[CD33]] may be expressed | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD41]]''' | |||
|colspan="1" style = "font-size:84%;"|Platelet glycoprotein IIbIIIa | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD61]]''' | |||
|colspan="1" style = "font-size:84%;"|Platelet glycoprotein IIIa | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD42b]]''' | |||
|colspan="1" style = "font-size:84%;"|Platelet gycoprotein Ib | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD36]]''' | |||
|colspan="1" style = "font-size:84%;"|Relatively non-specific (seen in erythroid and monocytic leukaemias) but often strongly expressed | |||
</span> | |||
|} | |||
</div> | |||
---- | |||
'''WHEN SHOULD ALTERNATIVE OR AMBIGUOUS LINEAGE BE ASSIGNED?''' | |||
This occurs if: | |||
*'''Any myeloid lineage-defining''' markers are present ''and'' '''B-Lymphoid and/or T-lymphoid defining markers''' are also present | |||
or | |||
*'''At least two myeloid lineage-associated markers are present''' ''but also'' ''''two markers of B-lymphoid and/or T-lymphoid lineage''' | |||
OR | |||
*Cells have '''no more than one lineage-associated''' marker of any lineage | |||
---- | |||
'''Sections''' | |||
*<span style="font-size:90%;>Markers of "primitive nature": [[#anchor_0|go to section]]</span> | |||
*<span style="font-size:90%;>Core markers of most cases: [[#anchor_1|go to section]]</span> | |||
*<span style="font-size:90%;>Aberrant markers often seen: [[#anchor_3|go to section]]</span> | |||
*<span style="font-size:90%;>Notes 1: specific subtypes: [[#anchor_4|go to section]]</span> | |||
*<span style="font-size:90%;>Notes 2: ambiguous lineage [[#anchor_5|go to section]]</span> | |||
<span style="font-size:90%;>('''note''': for further information on any marker or section click the blue highlighted text)</span> | |||
</div> | |||
---- | |||
---- | |||
---- | |||
<span id="anchor_1"></span>. | |||
<div style="width: 100%; border: 1px solid black; font-size:100%"> | |||
{| class="wikitable" style="color:black; background-color:#ffffff;" cellpadding="0" | |||
!colspan="2" <span style="font-size:90%; colour:white; text-align:center; border: 1px solid black; background:pale gray">|'''OTHER MARKERS OF MYELOID LINEAGE'''</span><span style="font-size:90%; text-align:left; background:white"> | |||
|- | |||
!colspan="2" style = "font-size:90%; background:#ddeee1"|While most cases of AML will be diagnosed using MPO, CD117, CD13 and CD33, some cases may be more difficult, particularly those significant differentation. In those cases supplementary antibodies may be helpful to make a diagnosis or confirm a pattern of differentation. | |||
<div class="mw-collapsible mw-collapsed" data-expandtext="Click for explanation" data-collapsetext="Hide explanation"> | |||
<div class="mw-collapsible-content"> | |||
<span style="font-size:90%;></br>Some additional markers are regarded as indicating primitive nature when expressed by AML blasts; these markers may be more usually assocated with T-lineage or B-lineage ALL, but when expressed in AML they are considered to indicate less differentiated forms.</br> | |||
</span> | |||
</div></div></div> | |||
|- | |||
!colspan="2" style = "font-size:90%;background:white;"|Granulocytic lineage markers | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD10]]''' | |||
|colspan="1" style = "font-size:84%;"|One of tne of the first lineage-markers acquired in AML with good relative specificity | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD11b]]''' | |||
|colspan="1" style = "font-size:84%;"|One of tne of the first lineage-markers acquired in AML with good relative specificity | |||
|- | |||
!colspan="2" style = "font-size:90%;background:white;"|Monocytic lineage markers | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD11c]]''' | |||
|colspan="1" style = "font-size:84%;"|One of tne of the first lineage-markers acquired in AML with good relative specificity | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD14]]''' | |||
|colspan="1" style = "font-size:84%;"|A good marker for AML that is often less strongly expressed in monocytic forms | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD64]]''' | |||
|colspan="1" style = "font-size:84%;"|A good lineage marker for AML aquired a little later, higher than CD13 in monocytic forms | |||
|- | |||
!colspan="2" style = "font-size:90%;background:white;"|'''Features associated with erythroid differentiation''' | |||
|- | |||
|colspan="2" style = "font-size:90%;background:white;"|Most often [[CD34]], [[CD45]] and [[HLA-DR]] are weak or negative, although [[CD117]] and [[CD36]] are generally expressed. There may be some expression of platelet markers in some cases. | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD71]]''' | |||
|colspan="1" style = "font-size:84%;"|Frequently expressed though not fully lineage specific | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD235]]''' | |||
|colspan="1" style = "font-size:84%;"|A good marker of erythroid differentiation but acquired late and therefore may not be expressed | |||
|- | |||
!colspan="2" style = "font-size:90%;background:white;"|'''Features associated with megakaryocytic differentiation''' | |||
|- | |||
|colspan="2" style = "font-size:90%;background:white;"|Most often [[CD34]], [[CD45]] and [[HLA-DR]] are weak or negative, although [[CD13]] and [[CD33]] may be expressed | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD41]]''' | |||
|colspan="1" style = "font-size:84%;"|Platelet glycoprotein IIbIIIa | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD61]]''' | |||
|colspan="1" style = "font-size:84%;"|Platelet glycoprotein IIIa | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD42b]]''' | |||
|colspan="1" style = "font-size:84%;"|Platelet gycoprotein Ib | |||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''[[CD36]]''' | |||
|colspan="1" style = "font-size:84%;"|Relatively non-specific (seen in erythroid and monocytic leukaemias) but often strongly expressed | |||
</span> | |||
|} | |||
</div> | |||
---- | |||
<span id="anchor_3"></span>. | |||
<div style="width: 100%; border: 1px solid black; font-size:100%"> | <div style="width: 100%; border: 1px solid black; font-size:100%"> | ||
{| class="wikitable" style="color:black; background-color:#ffffff;" cellpadding="0" | {| class="wikitable" style="color:black; background-color:#ffffff;" cellpadding="0" | ||
!colspan="2" <span style="font-size:90%; | !colspan="2" <span style="font-size:90%; colour:white; text-align:center; border: 1px solid black; background:pale gray">|'''NON MYELOID MARKERS FREQUENTLY "ABERENTLY" EXPRESSED IN AML'''</span> | ||
|- | |||
|colspan="2" style = "font-size:90%; color:black; background:#eedddd" |Markers of lymphoid lineage indicating primitive dfferentiation in AML | |||
<div class="mw-collapsible mw-collapsed" data-expandtext="Click for explanation" data-collapsetext="Hide explanation"> | <div class="mw-collapsible mw-collapsed" data-expandtext="Click for explanation" data-collapsetext="Hide explanation"> | ||
<div class="mw-collapsible-content"> | <div class="mw-collapsible-content"> | ||
<span style="font-size: | <span style="font-size:90%;></br>Some additional markers are regarded as indicating primitive nature when expressed by AML blasts; these markers may be more usually assocated with T-lineage or B-lineage ALL, but when expressed in AML they are considered to indicate less differentiated forms.</br> | ||
</span> | </span> | ||
</div></div></div> | </div></div></div> | ||
|- | |- | ||
|colspan=" | |colspan="1" style = "width: 4%; font-size:90%; color:black; background:white" |'''[[TDT]]''' | ||
|colspan="1" style = "font-size:80%; background:white;"|Expressed in some cases of AML (5-20%) particularly in less differentiated blast cells, often on a sub-population of cells. More typically associated with primitive ALL blast cells. | |||
|- | |- | ||
|colspan="1" style = "font-size:90%; color:black;" |'''[[ | |colspan="1" style = "font-size:90%; color:black; background:white" |'''[[CD7]]''' | ||
|colspan="1" style = "font-size: | |colspan="1" style = "font-size:80%;background:white "|Predominantly seen as a T-cell antigen, CD7 tends may be expressed by AML blasts (20-40%) where it most often indicates a more primitive forms or MPAL. CD7 is most consistently a marker of T-lineage (including T-ALL and more mature froms). | ||
|- | |- | ||
|colspan="2" style = "font-size:90%; color:black; background:# | |colspan="2" style = "font-size:90%; color:black; background:#eedddd" |Markers of lymphoid differentation abererantly expressed in AML | ||
<div class="mw-collapsible mw-collapsed" data-expandtext="Click for explanation" data-collapsetext="Hide explanation"> | |||
<div class="mw-collapsible-content"> | |||
<span style="font-size:90%;></br>Some additional markers are regarded as indicating primitive nature when expressed by AML blasts; these markers may be more usually assocated with T-lineage or B-lineage ALL, but when expressed in AML they are considered to indicate less differentiated forms.</br> | |||
</span> | |||
</div></div></div> | |||
|- | |- | ||
|colspan=" | |colspan="1" style = "width: 4%; font-size:90%; color:black; background:white" |'''[[TDT]]''' | ||
|colspan="1" style = "font-size:80%; background:white;"|Expressed in some cases of AML (5-20%) particularly in less differentiated blast cells, often on a sub-population of cells. More typically associated with primitive ALL blast cells. | |||
|- | |- | ||
|colspan="2" style = "font-size:90%;| | |colspan="1" style = "font-size:90%; color:black; background:white" |'''[[CD7]]''' | ||
|colspan="1" style = "font-size:80%;background:white "|Predominantly seen as a T-cell antigen, CD7 tends may be expressed by AML blasts (20-40%) where it most often indicates a more primitive forms or MPAL. CD7 is most consistently a marker of T-lineage (including T-ALL and more mature froms). | |||
|- | |||
|} | |||
</div></div> | |||
---- | |||
<span id="anchor_4"></span>. | |||
<div style="width: 100%; border: 1px solid black; font-size:100%"> | |||
{| class="wikitable" style="color:black; background-color:#ffffff;" cellpadding="0" | |||
!colspan="2" <span style="font-size:90%; text-align:center; border: 1px solid black; background:pale gray">|'''IMPORTANT ADDITIONAL POINTS 1'''</br></span> | |||
|- | |||
|colspan="2" style = "font-size:90%; color:black; background:#ddeee1" |AML subtypes with distinctive phenotype | |||
<div class="mw-collapsible mw-collapsed" data-expandtext="Click for explanation" data-collapsetext="Hide explanation"> | |||
<div class="mw-collapsible-content"> | |||
<span style="font-size:80%;></br>The first step in AML diagnosis to establish the primitive nature of the abnormal cells:</br> | |||
<span style="font-size:80%;>'''(1)''' Typically AML blasts have low CD45 expression and cause low side scatter. This means that they form a relatively uniform and distinctive population that is clearly separate from that of lymphocytes on CD45/SSc plots ([[CD45|for further details see this section]]) also not all AML forms may fit this pattern - particularly [[APL]] and [[monocytic AML]].</br> | |||
<span style="font-size:80%;>'''(2)''' Additional markers often expressed on myeloid cells may help confirm the primitive nature of the cells: in AML this is most often CD34, although other markers may contribute.</br> | |||
</span> | |||
</div></div></div> | |||
|- | |||
|colspan="2" style = "font-size:90%; color:black;" |'''Mixed Phenotype Acute leukaemia (MPAL)''' | |||
|- | |||
|colspan="2" style = "font-size:84%;"|Formerly known as leukaemia of ambiguous lineage | |||
|- | |||
|colspan="2" style = "font-size:90%; color:black;" |'''Early T-precursor acute lymphoblastic leukaemia (ETP-ALL)''' | |||
|- | |||
|colspan="2" style = "font-size:84%;"|A (relatively new entity) | |||
|- | |- | ||
|} | |} | ||
</div> | </div> | ||
---- | |||
<span id="anchor_5"></span>. | |||
<div style="width: 100%; border: 1px solid black; font-size:100%"> | <div style="width: 100%; border: 1px solid black; font-size:100%"> | ||
{| class="wikitable" style="color:black; background-color:#ffffff;" cellpadding="0" | {| class="wikitable" style="color:black; background-color:#ffffff;" cellpadding="0" | ||
!colspan="2" <span style="font-size:90%; | |||
!colspan="2" <span style="font-size:90%; text-align:center; border: 1px solid black; background:pale gray">|'''IMPORTANT ADDITIONAL POINTS 2'''</br></span> | |||
|- | |||
|colspan="2" style = "font-size:90%; color:black; background:#ddeee1" |'''Acute leukaemias with ambiguous lineage features''' | |||
<div class="mw-collapsible mw-collapsed" data-expandtext="Click for explanation" data-collapsetext="Hide explanation"> | <div class="mw-collapsible mw-collapsed" data-expandtext="Click for explanation" data-collapsetext="Hide explanation"> | ||
<div class="mw-collapsible-content"> | <div class="mw-collapsible-content"> | ||
<span style="font-size:80%; | <span style="font-size:80%;></br>The first step in AML diagnosis to establish the primitive nature of the abnormal cells:</br> | ||
<span style="font-size:80%;>'''(1)''' Typically AML blasts have low CD45 expression and cause low side scatter. This means that they form a relatively uniform and distinctive population that is clearly separate from that of lymphocytes on CD45/SSc plots ([[CD45|for further details see this section]]) also not all AML forms may fit this pattern - particularly [[APL]] and [[monocytic AML]].</br> | |||
<span style="font-size:80%;>'''(2)''' Additional markers often expressed on myeloid cells may help confirm the primitive nature of the cells: in AML this is most often CD34, although other markers may contribute.</br> | |||
</span> | </span> | ||
</div></div></div> | </div></div></div> | ||
|- | |- | ||
|colspan="2" style = "font-size:90%; color:black; | |colspan="2" style = "font-size:90%; color:black;" |'''Mixed Phenotype Acute leukaemia (MPAL)''' | ||
|- | |- | ||
|colspan=" | |colspan="2" style = "font-size:84%;"|Formerly known as leukaemia of ambiguous lineage: Myeloid MPO or monocytic defined by at least two markers (CD14, CD11c, CD64, NSE, lysozyme. T lineage CD3 (s or m), STRONG Cd19, with strong CD79a cCD22 or CD10 OR wk CD19 also with obove | ||
|- | |- | ||
|colspan=" | |colspan="2" style = "font-size:90%; color:black;" |'''Early T-precursor acute lymphoblastic leukaemia (ETP-ALL)''' | ||
|- | |- | ||
|colspan="2" style = "font-size: | |colspan="2" style = "font-size:84%;"|A (relatively new entity) | ||
|- | |- | ||
|colspan="2" style = "font-size:90%;| | |colspan="2" style = "font-size:90%; color:black;" |'''Undifferentiated acute leukaeemia''' | ||
|- | |- | ||
|colspan="2" style = "font-size: | |colspan="2" style = "font-size:84%;"|A (relatively new entity) | ||
|- | |||
|colspan="2" style = "font-size:90%; color:black;" |'''Non-haematopoietic tumours''' | |||
|- | |||
|colspan="2" style = "font-size:84%;"|need to know problems | |||
|- | |- | ||
|} | |} | ||
</div> | </div> | ||
---- |
Revision as of 18:48, 10 October 2023
SECTION 1: Establishing the primitive nature of the blast cells in AML
The recognition of blast cells requires them to have features of primitive phenotype, markers can help support this, although morphology may also be required
The expression of some markers is typically associated with primitive cells and can help recognise the primitive nature of blast cells. These markers may also have some lineage specificity.
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MARKERS USEFUL TO CONFIRM PRIMITIVE NATURE OF BLAST CELLS IN AML | |
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These markers are useful to recognise the primitive nature of cells rather than specific lineage
| |
CD45 | A marker expressed by all leukocytes and their precursors. In AML expression is characteristically "weak" i.e. significantly less intense than normal lymphocytes or monocytes. In monocytic AML expression may be stronger. |
CD34 | Frequently expressed by AML blast cells (40-80% of cases) - most often in less differentiated forms of AML. Expression is also seen frequently (and often more strongly) in ALL |
Other markers that may be associated with primitive nature in AML | |
In the context of a proven AML diagnosis a number of markers may be expressed that are considered to predominantly reflect the primitive nature of the cells. Some of these are more frequently associated with lymphoid disorders, but providing other criteria for AML are met they should simply be considered to show "primitivity". These include: CD38, HLA-DR, TDT, CD7. |
SECTION 2: Assigning blast cells as myeloid lineage
Essentially, leukaemic cells can be assigned solely to myeloid lineage under one of two circumstances:
1: A myeloid lineage-defining marker is expressed and no B or T-lineage defining markers are expressed
.
MYELOID-LINEAGE-DEFINING MARKERS | |
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The present WHO classification recognises only one marker as lineage-defining in AML
| |
MPO | A lineage-defining marker in AML when expressed (around 80% of cases). More frequent in cases with granulocytic maturation. When detected by flow cytometry is diagnostic of myeloid differentiation is established (either AML or MPAL) |
2: At least two myeloid-associated markers are expressed, and lineage cannot be assigned as B cell or T cell by lineage-specific or lineage-associated lymphoid markers
.
MYELOID-LINEAGE ASSOCIATED MARKERS (general) | |
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Each of these markers is frequently expressed in AML (80% of cases). They support a diagnosis of myeloid lineage, but are not sufficiently specific to be AML-defining when expressed alone
| |
CD117 | An early marker of myeloid lineage, seen in up to 80% of AML and vauable in recognising more primitive differentaiion forms (note that aberrant expression is seen in up to 20% of ALL cases) |
CD33 | A good marker for AML, particularly for those cases with granulocytic maturation, CD33 is often less strongly expressed in AML with monocytic dfferentiation and strongly expressed in APL. |
CD13 | A good lineage marker for AML that is acquired a little later in differentation than CD117 or CD33; expression of CD13 is often higher than CD33 in AML with monocytic differentiation. |
The markers already decribed are sufficient to make a diagnosis of typical AML in most cases. Typically the markers in this table are associated with specific features of differentiation so will not be present in all cases, but may be helpful as "lineage-assocated" markers in difficult cases. Care should be taken when doing so, since in some cases specificity may be lower than for typical myeloid markers.
.
MYELOID LINEAGE MARKER ASSOCIATED WITH SPECIFIC DIFFERENTIATION | |
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While most cases of AML will be diagnosed using MPO, CD117, CD13 and CD33, some cases may be more difficult, particularly those significant differentation. In those cases supplementary antibodies may be helpful to make a diagnosis or confirm a pattern of differentation.
| |
Granulocytic lineage markers | |
CD10 | Most frequently a marker expressed in ALL subtypes, but expression of CD10 may occur some more differentiated cases of AML (particularly APL and AML with monocytic maturation |
CD11b | One of tne of the first lineage-markers acquired in AML with good relative specificity |
Monocytic lineage markers | |
CD11c | One of tne of the first lineage-markers acquired in AML with good relative specificity |
CD14 | A good marker for AML that is often less strongly expressed in monocytic forms |
CD64 | A good lineage marker for AML aquired a little later, higher than CD13 in monocytic forms |
Features associated with erythroid differentiation | |
Most often CD34, CD45 and HLA-DR are weak or negative, although CD117 and CD36 are generally expressed. There may be some expression of platelet markers in some cases. | |
CD71 | Frequently expressed though not fully lineage specific |
CD235 | A good marker of erythroid differentiation but acquired late and therefore may not be expressed |
Features associated with megakaryocytic differentiation | |
Most often CD34, CD45 and HLA-DR are weak or negative, although CD13 and CD33 may be expressed | |
CD41 | Platelet glycoprotein IIbIIIa |
CD61 | Platelet glycoprotein IIIa |
CD42b | Platelet gycoprotein Ib |
CD36 | Relatively non-specific (seen in erythroid and monocytic leukaemias) but often strongly expressed
|
.
OTHER MARKERS OF MYELOID LINEAGE | |
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While most cases of AML will be diagnosed using MPO, CD117, CD13 and CD33, some cases may be more difficult, particularly those significant differentation. In those cases supplementary antibodies may be helpful to make a diagnosis or confirm a pattern of differentation.
| |
Granulocytic lineage markers | |
CD10 | One of tne of the first lineage-markers acquired in AML with good relative specificity |
CD11b | One of tne of the first lineage-markers acquired in AML with good relative specificity |
Monocytic lineage markers | |
CD11c | One of tne of the first lineage-markers acquired in AML with good relative specificity |
CD14 | A good marker for AML that is often less strongly expressed in monocytic forms |
CD64 | A good lineage marker for AML aquired a little later, higher than CD13 in monocytic forms |
Features associated with erythroid differentiation | |
Most often CD34, CD45 and HLA-DR are weak or negative, although CD117 and CD36 are generally expressed. There may be some expression of platelet markers in some cases. | |
CD71 | Frequently expressed though not fully lineage specific |
CD235 | A good marker of erythroid differentiation but acquired late and therefore may not be expressed |
Features associated with megakaryocytic differentiation | |
Most often CD34, CD45 and HLA-DR are weak or negative, although CD13 and CD33 may be expressed | |
CD41 | Platelet glycoprotein IIbIIIa |
CD61 | Platelet glycoprotein IIIa |
CD42b | Platelet gycoprotein Ib |
CD36 | Relatively non-specific (seen in erythroid and monocytic leukaemias) but often strongly expressed
|
WHEN SHOULD ALTERNATIVE OR AMBIGUOUS LINEAGE BE ASSIGNED?
This occurs if:
- Any myeloid lineage-defining markers are present and B-Lymphoid and/or T-lymphoid defining markers are also present
or
- At least two myeloid lineage-associated markers are present but also 'two markers of B-lymphoid and/or T-lymphoid lineage
OR
- Cells have no more than one lineage-associated marker of any lineage
Sections
- Markers of "primitive nature": go to section
- Core markers of most cases: go to section
- Aberrant markers often seen: go to section
- Notes 1: specific subtypes: go to section
- Notes 2: ambiguous lineage go to section
(note: for further information on any marker or section click the blue highlighted text)
.
OTHER MARKERS OF MYELOID LINEAGE | |
---|---|
While most cases of AML will be diagnosed using MPO, CD117, CD13 and CD33, some cases may be more difficult, particularly those significant differentation. In those cases supplementary antibodies may be helpful to make a diagnosis or confirm a pattern of differentation.
| |
Granulocytic lineage markers | |
CD10 | One of tne of the first lineage-markers acquired in AML with good relative specificity |
CD11b | One of tne of the first lineage-markers acquired in AML with good relative specificity |
Monocytic lineage markers | |
CD11c | One of tne of the first lineage-markers acquired in AML with good relative specificity |
CD14 | A good marker for AML that is often less strongly expressed in monocytic forms |
CD64 | A good lineage marker for AML aquired a little later, higher than CD13 in monocytic forms |
Features associated with erythroid differentiation | |
Most often CD34, CD45 and HLA-DR are weak or negative, although CD117 and CD36 are generally expressed. There may be some expression of platelet markers in some cases. | |
CD71 | Frequently expressed though not fully lineage specific |
CD235 | A good marker of erythroid differentiation but acquired late and therefore may not be expressed |
Features associated with megakaryocytic differentiation | |
Most often CD34, CD45 and HLA-DR are weak or negative, although CD13 and CD33 may be expressed | |
CD41 | Platelet glycoprotein IIbIIIa |
CD61 | Platelet glycoprotein IIIa |
CD42b | Platelet gycoprotein Ib |
CD36 | Relatively non-specific (seen in erythroid and monocytic leukaemias) but often strongly expressed
|
.
NON MYELOID MARKERS FREQUENTLY "ABERENTLY" EXPRESSED IN AML | |
---|---|
Markers of lymphoid lineage indicating primitive dfferentiation in AML
| |
TDT | Expressed in some cases of AML (5-20%) particularly in less differentiated blast cells, often on a sub-population of cells. More typically associated with primitive ALL blast cells. |
CD7 | Predominantly seen as a T-cell antigen, CD7 tends may be expressed by AML blasts (20-40%) where it most often indicates a more primitive forms or MPAL. CD7 is most consistently a marker of T-lineage (including T-ALL and more mature froms). |
Markers of lymphoid differentation abererantly expressed in AML
| |
TDT | Expressed in some cases of AML (5-20%) particularly in less differentiated blast cells, often on a sub-population of cells. More typically associated with primitive ALL blast cells. |
CD7 | Predominantly seen as a T-cell antigen, CD7 tends may be expressed by AML blasts (20-40%) where it most often indicates a more primitive forms or MPAL. CD7 is most consistently a marker of T-lineage (including T-ALL and more mature froms). |
.
IMPORTANT ADDITIONAL POINTS 1 | |
---|---|
AML subtypes with distinctive phenotype
(1) Typically AML blasts have low CD45 expression and cause low side scatter. This means that they form a relatively uniform and distinctive population that is clearly separate from that of lymphocytes on CD45/SSc plots (for further details see this section) also not all AML forms may fit this pattern - particularly APL and monocytic AML. | |
Mixed Phenotype Acute leukaemia (MPAL) | |
Formerly known as leukaemia of ambiguous lineage | |
Early T-precursor acute lymphoblastic leukaemia (ETP-ALL) | |
A (relatively new entity) |
.
IMPORTANT ADDITIONAL POINTS 2 | |
---|---|
Acute leukaemias with ambiguous lineage features
(1) Typically AML blasts have low CD45 expression and cause low side scatter. This means that they form a relatively uniform and distinctive population that is clearly separate from that of lymphocytes on CD45/SSc plots (for further details see this section) also not all AML forms may fit this pattern - particularly APL and monocytic AML. | |
Mixed Phenotype Acute leukaemia (MPAL) | |
Formerly known as leukaemia of ambiguous lineage: Myeloid MPO or monocytic defined by at least two markers (CD14, CD11c, CD64, NSE, lysozyme. T lineage CD3 (s or m), STRONG Cd19, with strong CD79a cCD22 or CD10 OR wk CD19 also with obove | |
Early T-precursor acute lymphoblastic leukaemia (ETP-ALL) | |
A (relatively new entity) | |
Undifferentiated acute leukaeemia | |
A (relatively new entity) | |
Non-haematopoietic tumours | |
need to know problems |