Acute leukaemia types: Difference between revisions
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<div class="mw-collapsible mw-collapsed" data-expandtext="Initial Considerations: before diagnosing acute leukaemia by flow" data-collapsetext="Hide details"> | <div class="mw-collapsible mw-collapsed" data-expandtext="Initial Considerations: before diagnosing acute leukaemia by flow" data-collapsetext="Hide details"> | ||
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<span style="color: navy>''Before assigning a myeloid or lymphoid phenotype to the abnormal cells it is important to establish whether cells are leukaemic blasts. Several methods may be applied''</span> | <span style="color: navy>''Before assigning a myeloid or lymphoid phenotype to the abnormal cells it is important to establish whether cells are leukaemic blasts. Several methods may be applied''</span> | ||
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*The cells should have morphological features of leukaemic blasts | *The cells should have morphological features of leukaemic blasts | ||
*The clinical background should be consistent with acute leukaemia | *The clinical background should be consistent with acute leukaemia | ||
*Immuophenotypic features of "primitive" phenotype should be identified | *Immuophenotypic features of "primitive" phenotype should be identified | ||
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<div class="mw-collapsible mw-collapsed" data-expandtext="2. Initial Considerations: before diagnosing acute leukaemia by flow" data-collapsetext="Hide details"> | |||
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<span style="color: navy>''After phenotyping the cells flow cytometric findings may be modified by other investigations:'' | <span style="color: navy>''After phenotyping the cells flow cytometric findings may be modified by other investigations:'' | ||
*Markers found on trephine may identify features of alternative lineage | *Markers found on trephine may identify features of alternative lineage | ||
*Cytogenetic features may identify a specific type of leukaemia | *Cytogenetic features may identify a specific type of leukaemia | ||
*Genetic features may assign a specific lineage or type | *Genetic features may assign a specific lineage or type | ||
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Revision as of 17:57, 5 October 2023
NOTE: the flow cytometric typing of acute leukaemia should always be regarded as provisional. It can direct initial treatment, but lineage, blast cell count and occasionally leukaemia type may be subject to modification as other evidence emerges.
Before assigning a myeloid or lymphoid phenotype to the abnormal cells it is important to establish whether cells are leukaemic blasts. Several methods may be applied
- The cells should have morphological features of leukaemic blasts
- The clinical background should be consistent with acute leukaemia
- Immuophenotypic features of "primitive" phenotype should be identified
After phenotyping the cells flow cytometric findings may be modified by other investigations:
- Markers found on trephine may identify features of alternative lineage
- Cytogenetic features may identify a specific type of leukaemia
- Genetic features may assign a specific lineage or type
(1) Myeloid lineage-defining markers are present without B or T-lineage defining markers
(2) At least two myeloid-associated antigens are expressed, and no other lineage can be defined
Consider alternative diagnosis if:
(1) Myeloid lineage-defining markers are present AND B-Lymphoid and/or T-lymphoid defining markers are also present
(2) At least two myeloid lineage-associated markers are present but also two markers of B-lymphoid and/or T-lymphoid lineage
(3) Cells have no more than one 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)
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MARKERS USEFUL TO CONFIRM PRIMITIVE NATURE OF BLAST CELLS | |
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Useful markers of primitive nature
(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). 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. | |
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 seein 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 their presence does not change lineage assignment of AML. These include CD38, HLA-DR, TDT, CD7. |
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MARKERS USEFUL TO CONFIRM MYELOID LINEAGE OR DIFFERENTIATION | |
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Frequently expressed "general" markers of myeloid lineage
| |
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 (either AML or MPAL) |
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. |
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MARKERS USEFUL TO CONFIRM MYELOID LINEAGE OR DIFFERENTIATION | |
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Confirmatory markers of AML or markers of subtype
| |
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
|
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NON MYELOID MARKERS FREQUENTLY "ABERENTLY" EXPRESSED IN AML | |
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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). |
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IMPORTANT ADDITIONAL POINTS 1 | |
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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) |
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IMPORTANT ADDITIONAL POINTS 2 | |
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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 |