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| ----
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| '''Sections'''
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| *<span style="font-size:90%;>Markers of "primitive nature": [[#anchor_0|go to section]]</span>
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| *<span style="font-size:90%;>Core markers of most cases: [[#anchor_1|go to section]]</span>
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| *<span style="font-size:90%;>Aberrant markers often seen: [[#anchor_3|go to section]]</span>
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| *<span style="font-size:90%;>Notes 1: specific subtypes: [[#anchor_4|go to section]]</span>
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| *<span style="font-size:90%;>Notes 2: ambiguous lineage [[#anchor_5|go to section]]</span>
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| <span style="font-size:90%;>('''note''': for further information on any marker or section click the blue highlighted text)</span>
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| </div>
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| ----
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|
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| <span id="anchor_0"></span>. | | <span id="anchor_0"></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%; font-color:navy; text-align:center; border: 1px solid black; background:pale gray">|'''MARKERS USEFUL TO CONFIRM PRIMITIVE NATURE OF BLAST CELLS'''</br></span> | | !colspan="2" <span style="font-size:90%; font-color:navy; text-align:center; border: 1px solid black; background:pale gray">|'''Lineage assignments 1 - defining Myeloid lineage in MPAL'''</br></span> |
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| |colspan="2" style = "font-size:90%; color:black; background:#ddeee1" |'''Useful markers of primitive nature'''
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| <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%;></br>The first step in AML diagnosis to establish the primitive nature of the abnormal cells:</br> | | <span style="font-size:80%;></br>The first step in AML diagnosis to establish the primitive nature of the abnormal cells:</br> |
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| <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 may fit this pattern low CD45/low SSc pattern - particularly [[APL]] and [[monocytic AML]].</br></span> | | <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 may fit this pattern low CD45/low SSc 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 and are also listed.</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 and are also listed.</br> |
| </span> | | </span> |
| </div></div></div> | | </div></div></div> |
| |- | | |- |
| |colspan="1" style = "font-size:90%; color:black;" |'''[[CD45]]'''
| | |colspan="2" style = "font-size:90%; color:black; background:#ddeee1" |'''Myeloid markers option 1''' |
| |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.
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| |-
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| |colspan="1" style = "font-size:90%; color:black;" |'''[[CD34]]'''
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| |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 seein frequently (and often more strongly) in ALL'''
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| |-
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| |colspan="2" style = "font-size:90%; color:black; background:#eedddd" |Other markers that may be associated with primitive nature in AML
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| |-
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| |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 their primitive nature. Some of these are more frequently associated with lymphoid disorders, but providing other criteria for AML are met their presence does not change lineage assignment. These include [[TDT]], [[CD7]], other?
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| |}
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| </div>
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| ----
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| <span id="anchor_1"></span>.
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| <div style="width: 100%; border: 1px solid black; font-size:100%">
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| {| class="wikitable" style="color:black; background-color:#ffffff;" cellpadding="0"
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| !colspan="2" <span style="font-size:90%; colour:white; text-align:center; border: 1px solid black; background:pale gray">|'''MARKERS USEFUL TO CONFIRM MYELOID LINEAGE OR DIFFERENTIATION'''</span><span style="font-size:90%; text-align:left; background:white">
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| |-
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| |colspan="2" style = "font-size:90%; color:black; background:#ddeee1" |'''Frequently expressed "general" markers of myeloid lineage''' | |
| <div class="mw-collapsible mw-collapsed" data-expandtext="Click for explanation" data-collapsetext="Hide explanation">
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| <div class="mw-collapsible-content">
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| <span style="font-size:90%;></br>These markers may be considered the most frequent set of markers expressed by AML. Having said that the expression of any single marker is not required for the diagnosis of AML and it is recognised that ('''excluding MPO'''), and each may be expressed by cells of ALL. General concepts:
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| * Expression of MPO is lineage defining and should indicate AML (or [[MPAL]] if lymphoid lineage also confirmed)
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| * In the absence of markers suggesting alternative lineage any of the remaining markers (CD117, CD33, CD13) may (alone) be used to support a diagnosis of AML
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| * Expression of one or more of CD117, CD33, CD13 markers on otherwise typical ALL is allowed and does not change lineage assignment
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| </br>
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| </span>
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| </div></div></div>
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| |- | | |- |
| |colspan="1" style = "font-size:90%; color:black;" |'''[[MPO]]''' | | |colspan="1" style = "font-size:90%; color:black;" |'''[[MPO|Myeloperoxidase (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 (either AML or MPAL) | | |colspan="1" style = "font-size:90%;"|This marker alone is sufficient to establish myeloid lineage provided it meets the intensity definition - intensity should be at least half of that of mature neutrophils in at least of proportion of cells. |
| |- | | |- |
| |colspan="1" style = "font-size:90%; color:black;" |'''[[CD117]]''' | | |colspan="2" style = "font-size:90%; color:black; background:#ddeee1" |'''Myeloid markers option 2''' |
| |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)
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| |- | | |- |
| |colspan="1" style = "font-size:90%; color:black;" |'''[[CD33]]''' | | |colspan="2" style = "font-size:90%;|If MPO does not meet criteria for myeloid lineage, then myeloid lineage may still be assigned through demonstration of monocytic lineage. This can be assigned by the detection of '''AT LEAST TWO''' of the following |
| |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.
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| |- | | |- |
| |colspan="1" style = "font-size:90%; color:black;" |'''[[CD13]]''' | | |colspan="2" style = "font-size:90%;|Surface markers of monocytic lineage: [[CD11c]], [[CD14]], [[CD64]] or Other recognised features of monocytic differentiation: '''serum or urinary lysozyme''' or '''non-specific esterase''' (detected by enzyme cytochemistry) |
| |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.
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| |- | | |- |
| |} | | |} |
| </div> | | </div> |
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| ----
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|
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| <span id="anchor_1"></span>. | | <span id="anchor_0"></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%; colour:white; text-align:center; border: 1px solid black; background:pale gray">|'''MARKERS USEFUL TO CONFIRM MYELOID LINEAGE OR DIFFERENTIATION'''</span><span style="font-size:90%; text-align:left; background:white"> | | !colspan="2" <span style="font-size:90%; font-color:navy; text-align:center; border: 1px solid black; background:pale gray">|'''Lineage assignments 2 - defining B-lymphoid lineage in MPAL'''</br></span> |
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| !colspan="2" style = "font-size:90%; background:#ddeee1"|Confirmatory markers of AML or markers of subtype
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| <div class="mw-collapsible mw-collapsed" data-expandtext="Click for explanation" data-collapsetext="Hide explanation">
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| <div class="mw-collapsible-content">
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| <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>
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| </span>
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| </div></div></div>
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| |-
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| !colspan="2" style = "font-size:90%;background:white;"|Granulocytic lineage markers
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| |-
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| |colspan="1" style = "font-size:90%; color:black;" |'''[[CD10]]'''
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| |colspan="1" style = "font-size:84%;"|One of tne of the first lineage-markers acquired in AML with good relative specificity
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| |-
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| |colspan="1" style = "font-size:90%; color:black;" |'''[[CD11b]]'''
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| |colspan="1" style = "font-size:84%;"|One of tne of the first lineage-markers acquired in AML with good relative specificity
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| |-
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| !colspan="2" style = "font-size:90%;background:white;"|Monocytic lineage markers
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| |-
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| |colspan="1" style = "font-size:90%; color:black;" |'''[[CD11c]]'''
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| |colspan="1" style = "font-size:84%;"|One of tne of the first lineage-markers acquired in AML with good relative specificity
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| |-
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| |colspan="1" style = "font-size:90%; color:black;" |'''[[CD14]]'''
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| |colspan="1" style = "font-size:84%;"|A good marker for AML that is often less strongly expressed in monocytic forms
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| |-
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| |colspan="1" style = "font-size:90%; color:black;" |'''[[CD64]]'''
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| |colspan="1" style = "font-size:84%;"|A good lineage marker for AML aquired a little later, higher than CD13 in monocytic forms
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| |-
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| !colspan="2" style = "font-size:90%;background:white;"|Erythroid lineage markers
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| |-
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| |colspan="1" style = "font-size:90%; color:black;" |'''[[CD14]]'''
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| |colspan="1" style = "font-size:84%;"|A good marker for AML that is often less strongly expressed in monocytic forms
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| |-
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| |colspan="1" style = "font-size:90%; color:black;" |'''[[CD64]]'''
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| |colspan="1" style = "font-size:84%;"|A good lineage marker for AML aquired a little later, higher than CD13 in monocytic forms
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| |-
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| !colspan="2" style = "font-size:90%;background:white;"|Megakaryocytic lineage markers
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| |-
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| |colspan="1" style = "font-size:90%; color:black;" |'''[[CD14]]'''
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| |colspan="1" style = "font-size:84%;"|A good marker for AML that is often less strongly expressed in monocytic forms
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| |-
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| |colspan="1" style = "font-size:90%; color:black;" |'''[[CD64]]'''
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| |colspan="1" style = "font-size:84%;"|A good lineage marker for AML aquired a little later, higher than CD13 in monocytic forms
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| </span>
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| |}
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| </div>
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| ----
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| | |
| <span id="anchor_3"></span>.
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| <div style="width: 100%; border: 1px solid black; font-size:100%">
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| {| class="wikitable" style="color:black; background-color:#ffffff;" cellpadding="0"
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| !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>
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| |-
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| |colspan="2" style = "font-size:90%; color:black; background:#eedddd" |Markers of lymphoid lineage indicating primitive dfferentiation in AML
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| <div class="mw-collapsible mw-collapsed" data-expandtext="Click for explanation" data-collapsetext="Hide explanation">
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| <div class="mw-collapsible-content">
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| <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>
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| </span>
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| </div></div></div>
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| |-
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| |colspan="1" style = "width: 4%; font-size:90%; color:black; background:white" |'''[[TDT]]'''
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| |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.
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| |-
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| |colspan="1" style = "font-size:90%; color:black; background:white" |'''[[CD7]]'''
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| |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).
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| |-
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| |colspan="2" style = "font-size:90%; color:black; background:#eedddd" |Markers of lymphoid differentation abererantly expressed in AML
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| <div class="mw-collapsible mw-collapsed" data-expandtext="Click for explanation" data-collapsetext="Hide explanation">
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| <div class="mw-collapsible-content">
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| <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>
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| </span>
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| </div></div></div>
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| |-
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| |colspan="1" style = "width: 4%; font-size:90%; color:black; background:white" |'''[[TDT]]'''
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| |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.
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| |-
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| |colspan="1" style = "font-size:90%; color:black; background:white" |'''[[CD7]]'''
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| |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).
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| |-
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| |}
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| </div></div>
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| ----
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| <span id="anchor_4"></span>.
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| <div style="width: 100%; border: 1px solid black; font-size:100%">
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| {| class="wikitable" style="color:black; background-color:#ffffff;" cellpadding="0"
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| !colspan="2" <span style="font-size:90%; text-align:center; border: 1px solid black; background:pale gray">|'''IMPORTANT ADDITIONAL POINTS 1'''</br></span>
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| |-
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| |colspan="2" style = "font-size:90%; color:black; background:#ddeee1" |AML subtypes with distinctive phenotype
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| <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%;></br>The first step in AML diagnosis to establish the primitive nature of the abnormal cells:</br> | | <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%;>'''(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 may fit this pattern low CD45/low SSc 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 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 and are also listed.</br> |
| </span> | | </span> |
| </div></div></div> | | </div></div></div> |
| |- | | |- |
| |colspan="2" style = "font-size:90%; color:black;" |'''Mixed Phenotype Acute leukaemia (MPAL)''' | | |colspan="2" style = "font-size:90%; color:black; background:#ddeee1" |'''Marker combination 1''' |
| |- | | |- |
| |colspan="2" style = "font-size:84%;"|Formerly known as leukaemia of ambiguous lineage | | |colspan="1" style = "font-size:90%; color:black;"|'''[[CD19|Strong expression of CD19]]''' |
| | |colspan="1" style = "font-size:90%;"|To meet the definition of "strong" the expression intensity must exceed that of 50% of normal B lymphocytes |
| |- | | |- |
| |colspan="2" style = "font-size:90%; color:black;" |'''Early T-precursor acute lymphoblastic leukaemia (ETP-ALL)''' | | |colspan="1" style = "font-size:90%;"||Additional criteria must also be met: |
| | |colspan="1" style = "font-size:90%;"||There must be additional expression of at least one of the following [[CD10]], [[CD22]], or [[CD79a]] |
| |- | | |- |
| |colspan="2" style = "font-size:84%;"|A (relatively new entity) | | |colspan="2" style = "font-size:90%; color:black; background:#ddeee1" |'''Marker combination 2''' |
| |- | | |- |
| |} | | |colspan="2" style = "font-size:90%;|If MPO does not meet criteria for myeloid lineage, then myeloid lineage may still be assigned through demonstration of monocytic lineage. This can be assigned by the detection of '''AT LEAST TWO''' of the following |
| </div>
| |
| | |
| ----
| |
| | |
| <span id="anchor_5"></span>.
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| <div style="width: 100%; border: 1px solid black; font-size:100%">
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| {| class="wikitable" style="color:black; background-color:#ffffff;" cellpadding="0"
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| !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''' | | |colspan="2" style = "font-size:90%;|Surface markers of monocytic lineage: [[CD11c]], [[CD14]], [[CD64]] or Other recognised features of monocytic differentiation: '''serum or urinary lysozyme''' or '''non-specific esterase''' (detected by enzyme cytochemistry) |
| <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>
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| |-
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| |colspan="2" style = "font-size:90%; color:black;" |'''Mixed Phenotype Acute leukaemia (MPAL)'''
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| |-
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| |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
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| |-
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| |colspan="2" style = "font-size:90%; color:black;" |'''Early T-precursor acute lymphoblastic leukaemia (ETP-ALL)'''
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| |-
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| |colspan="2" style = "font-size:84%;"|A (relatively new entity)
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| |-
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| |colspan="2" style = "font-size:90%; color:black;" |'''Undifferentiated acute leukaeemia'''
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| |-
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| |colspan="2" style = "font-size:84%;"|A (relatively new entity)
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| |-
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| |colspan="2" style = "font-size:90%; color:black;" |'''Non-haematopoietic tumours'''
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| |-
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| |colspan="2" style = "font-size:84%;"|need to know problems
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| |- | | |- |
| |} | | |} |
| </div> | | </div> |
|
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| ----
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