- Myeloproliferative neoplasm containing the translocation t(9;22)(q34.1;q11.2) resulting in the BCR-ABL1 fusion gene, the Philadelphia chromosome (Ph).
- 90-95% of cases have the classic translocation.
- Small number of remaining cases may have a cryptic translocation (detected by FISH or RT-PCR).
- p210 – major breakpoint present in most cases.
- p230 – a larger fusion protein present in a small number of cases, which may have a more prominent neutrophilic component and/or thrombocytosis.
- p190 – minor breakpoint, frequently associated with ALL (can be seen in rare cases of CML with increased monocytes, which mimic CMML).
- Granulocytes are the predominate component (myelocyte bulge).
- Tyrosine kinase inhibitor (TKI) therapy has turned CML into a chronic disease.
Immunohistochemistry
The use of immunohistochemistry (IHC) in many of the myeloproliferative neoplasms is limited. Identifying an increased blast population is one of the most useful. Helpful IHC markers may include:
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Stain
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Comment
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CD34 marks immature cells including myeloblasts. In the setting of AML, it is ~70% sensitive. A subset of lymphoblasts may express CD34.
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CD117 is a specific myeloid marker, and marks a subset of myeloblasts. The expression is dim, and one often must look at 20-40X to clearly see expression. Mast cells (fried egg looking cell) will have very strong expression.
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CD71 marks nucleated erythroid cells. This may be helpful in quantitating and differentiating erythroid cells from myeloid cells. This marker may be set-up as a double stain with CD34.
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In the setting of hematopoietic cells, E-Cadherin marks immature erythroid cells. Like CD71, E-Cadherin may be useful to differentiate immature erythroid cells from immature myeloid cells.
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TdT is a sensitive lymphoblast (~95%) marker. It is not entirely specific for lymphoblasts, but other markers can help clarify diagnostic difficulties (B and T-cell markers). Approximately 20-30% of CML blast phase cases are lymphoblasts.
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References
Hematopathology. [edited by] Jaffe, ES. 1st. ed. Elsevier, Inc. © 2011.
Swerdlow SH, Campo E, Harris, NL, Jaffe ES, Pileri SA, Stein H, Thiele J (Eds): WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition). IARC: Lyon 2017