Molecular characterization ofde novoPhiladelphia chromosome-positive acute myeloid leukemia

Abstract

Philadelphia chromosome-positive (Ph+) AML is a controversial diagnosis, as others propose it represents CML in blast phase (CML-BP). NPM1 mutations occur in 25-35% of AML but are absent in CML patients. Conversely, ABL1 mutations occur in 25% of Imatinib-naïve CML-BP but are not described in AML patients. We analyzed for NPM1 and ABL1 mutations in 9 Ph+ AML and 5 CML-BP patients initially presented in BP. In 6 Ph+ AML cases, we screened for a panel of gene mutations using Sequenome®-based methods including AKT1, AKT2, AKT3, BRAF, EGFR, GNAQ, GNAS, IDH1, IDH2, KRAS, MET, NRAS, PIK3CA, and RET. Two of 9 (22%) Ph+ AML patients had NPM1 mutations and were alive 36 and 71 months after diagnosis. All Ph+ AML were negative for ABL1 and other gene mutations. One (20%) CML-BP patients had ABL1 mutation; no patients had NPM1 mutations. These data suggest that Ph+ AML is distinct from CML-BP.

The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia

“…Finally, a new provisional category of AML with BCR-ABL1 is added to recognize these rare de novo AML cases that may benefit from TKI therapy. 78,79 Although the diagnostic distinction between de novo AML with BCR-ABL1 and blast transformation of CML may be difficult without adequate clinical information, the significance of detecting this targetable fusion is felt to warrant a provisional disease category. Preliminary data suggest that deletion of antigen receptor genes (IGH, TCR), IKZF1 and/or CDKN2A may support a diagnosis of de novo disease vs BP of CML.…”

Allogeneic stem cell transplantation (allo-SCT) for de novo Ph+ AML: a study from the French Society of Bone Marrow Transplantation and Cell Therapy

“…4 In addition, cytogenetic and molecular abnormalities may be useful to distinguish CML from Ph+ AML 5 as much as trisomy 8, trisomy 19 or isochromosome 17q, besides t(9;22) and ABL1 mutations are common additional abnormalities in MBC-CML, 4,6,7 while Ph+ AML generally exhibits gene mutations suppressing cell differentiation (Core Binding Factor AML, NPM1) or mutations increasing cell proliferation (FLT3, RAS). 3,6,8 Primary Ph+ AML has recently been described as a distinct AML subtype with a specific genome signature compared with CML. 9 Although allogeneic stem cell transplantation (Allo-SCT) is often proposed as the curative option, the outcome of Ph+ AML treated with Allo-SCT remains unknown in the literature.…”

Philadelphia-Positive Acute Myeloblastic Leukemia: A Rare Entity

“…There is no significant difference in total leucocyte count, percentage of eosinophil's, or monocytes. There was also no difference in the number of megakaryocytes or in erythroid, myeloid, or megakaryocyte dysplasia [6][7][8]. There is also no difference in percentage and immune-phenotyping of blasts between the two groups.…”