Table 3.
Expression of cell-surface and cytoplasmic markers for the diagnosis of AML and MPAL
| Expression of cell-surface and cytoplasmic markers | |
|---|---|
| Diagnosis of AML* | |
| Precursors† | CD34, CD117, CD33, CD13, HLA-DR |
| Granulocytic markers‡ | CD65, cytoplasmic MPO |
| Monocytic markers§ | CD14, CD36, CD64 |
| Megakaryocytic markers|| | CD41 (glycoprotein IIb/IIIa), CD61 (glycoprotein IIIa) |
| Erythroid markers | CD235a (glycophorin A), CD36 |
| Diagnosis of MPAL¶ | |
| Myeloid lineage | MPO (flow cytometry, immunohistochemistry, or cytochemistry) or monocytic differentiation (at least 2 of the following: nonspecific esterase cytochemistry, CD11c, CD14, CD64, lysozyme) |
| T-lineage | Strong# cytoplasmic CD3 (with antibodies to CD3 ε chain) or surface CD3 |
| B-lineage** | Strong# CD19 with at least 1 of the following strongly expressed: cytoplasmic CD79a, cCD22, or CD10 or weak CD19 with at least 2 of the following strongly expressed: CD79a, cCD22, or CD10 |
MPO, myeloperoxidase. Other abbreviations are explained in Table 1.
The markers proposed in this table are according to European LeukemiaNet Work Package 10 recommendations.48
CD38 and other markers such as CD123 or CD133 can be added to identify leukemic stem cells, but do not contribute to diagnosis.
Of note, cells engaged in granulocytic maturation will retain the expression of CD13 and CD33 at various fluorescence levels. Seeking for the expression of CD15 and CD11b can provide further information. CD16 is only present on normal mature granulocytes. The absence of MPO together with myeloid markers defines AML with minimal differentiation which is different from acute undifferentiated leukemia.
Of note, cells engaged in monocytic differentiation will retain the expression of CD13 and CD33. Seeking the expression of CD64 and CD11b can provide additional information, notably for promonocytes.
CD42 (glycoprotein 1b) can also be used.
The category MPAL includes leukemias with expression of antigens of >1 lineage. They can either contain distinct blast populations of different lineages, or 1 blast population with expression of antigens of different lineages on the same cells, or a combination. The proposal in this table includes the modifications brought in the current update of the WHO classification of hematopoietic tumors.3,4
Strong defined as equal or brighter than the normal B or T cells in the sample.
Other markers can be used to confirm B-lineage involvement.