Can anyone tell me which parameters will differentiate if a 9:22 positive transcript arising from Blood or bone marrow is of CMA or AML case?
Hello,
The Ph translocation is the same, but CML is more likely to have splenomegaly, increased basophils, and possibly different cytogenetics. But the only true way is to look at the cells. You may find this article helpful:
A Rare Aggressive Leukemia With Clinicopathologic Features
Distinct From Chronic Myeloid Leukemia in Myeloid Blast Crisis
By cell morphology: AML has more than 20% of blast cells and a stop in the maturation of granulocytic lineage; CML has few blast cells and mielemia (cells from all the granulocytic maturation stages).
I hope Ur asking about CML in blast crisis versus AML.. Otherwise just the blast count is enough to differentiate the two... However, for CML-BC vs AML, The following should help...
History: CML has a longer history, with more non specific complaints especially early satiety, dragging left upper abd pain.
Examination: CML more likely to have massive splenomegaly, hepatomegaly
Routine blood tests incl. Peripheral smear: CML has higher cell count with a full range of immature myeloid cells in smear. This is called myeloid bulge. Basophilia is characteristic of CML. Blasts will not help as it can be seen in CML-blast crisis as well.
Bone marrow: phenomenon of myeloid bulge seen here as well with significant basophilia
Cell morphology: more immature forms seen in CML, larger size of cells, sometimes AML has characteristic features like auer rods, strong MPO positivity.
Cytogenetics: Both have the Philadelphia chromosome, but AML more likely to have added cytogenetic abnormalities.
Molecular subtype: break chain region fusion transcript is almost always p210 for CML.
The differentiation is done after taking all this into consideration. Even so, there may be instances where u still can't differentiate between the two. This is not necessarily a bad thing as the treatment of both is nearly the same.. With a standard induction remission protocol with a TKI followed by allogenic transplant at first remission. Prognosis is very poor for both but some studies have shown the AML with Ph positivity will do slightly better.
Ph+ AML is an entity which is somehow controversial. If patient does have an enlarged spleen, markedly high leukocytosis and basophilia, it is probably CML in blast phase (CML-BP). In addition, compared with the CML-BP, Ph+ AML is associated with the p210 BCR-ABL protein (vs p190 BCR-ABL protein), and the coexistence of normal metaphases in addition to Ph+ metaphases. The presence of dwarf megakaryocytes in bone marrow; additional cytogenetic aberrations, such as an extra copy of Ph chromosome, trisomies 8 and 19, and isochromosome 17q; and the persistence of t(9;22) after induction therapy are more common in CML-BP than in Ph+ AML. None of these features, however, are diagnostic of CML -BP or Ph+ AML.
Konoplev S, et al. Molecular characterization of de novo Ph+ Acute Myeloid Leukemia. Leuk Lymphoma. 2013; 54:138–144.
Bhatt VR, et al. Allogeneic stem cell transplantation for Philadelphia chromosome-positive acute myeloid leukemia. J Natl Compr Canc Netw. 2014l;12:963-968.
Ph +ve AML could be a blastic phase of CML, if not then following point can be differentiated,
1. No splenomegaly
2. No basophilia and/or eosinophilia
3. Comparative low TLC
4. Most important percentage of Ph +ve metaphases is in most of the cases below 90%.
FISH analysis in neutrophils (polynuclear cells) is useful for differentiating Ph+ALL or AML from CML-BC. Polynuclear cells in CML-BC harbors Ph chromosome but those in de novo Ph+ALL or Ph+AML do not have.
Just as highlighted above in this discussion, the differential diagnosis is between an AML and a CML in the blastic phase. Despite the basophilia in the PB can be crucial in this diagnostic process (basophilia is prominent in the CML-BF), the morphological differentiation can be very difficult in case of AML with t(6;9) which demonstrates an increase of basophils >2.0% in more of 50-60% of cases so, only the Pn negativity in the t(6;9) AML rule out this leukemic type from the differential reasoning.
Ph-positive AML is cytogenetically indistinguishable from Ph-positive CML, but molecular studies show that, in 50% of cases, the breakpoint on chromosome 22 in Ph-positive AML is different from those very consistently found in CML [Acta Haematol. 2002;107(2):76–94]. Furthermore, studies have confirmed that BCR-ABL1-positive AML is a unique acute leukemia with some features distinct from myeloid CML-BC. These features include less marked splenomegaly, fewer peripheral basophiles, and a lower myeloid/erythroid ratio, and bone marrow cellularity compared with myeloid CML-BC [J Clin Pathol. 2007;127(4):642–50]. In addition, the loss within the immunoglobulin genes (deletion of 14q32) in some cases of de novo Ph-positive AML can distinguish it from myeloid CML-BC [Brit J Haematol. 2013;161(4):541–50.]. However, the median survivals of Ph-positive AML and myeloid CML-BC patients are similar (9 vs. 7 months) [J Clin Pathol. 2007;127(4):642–50].
Source: Chinese Journal of Cancer 201635:48
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