Discussion:
CML is a form of myeloproliferative neoplasm (MPN) characterized by a balanced chromosomal translocation t(9; 22) (q34; q11.2), also known as the Philadelphia chromosome [1]. The resultant gene, BCR/ABL (breakpoint cluster region/Abelson gene, has tyrosine kinase activity that leads to abnormal growth of the cells [2,3]. CML accounts for about 15% of newly diagnosed cases of leukemia in adults [3].
AML with BCR/ABL+ had been included as a separate provisional entity in 2016 by WHO classification of myeloid neoplasms [1]. AML with BCR/ABL+ is considered to carry a worse prognosis, and hence its management approach is different from CML-BP [4]. There are overlapping clinical features between BCR-ABL + AML and myeloid CML blast crisis; moreover, there are no definite clinical criteria established yet to distinguish among these entities [4,5]. The involvement of molecular markers such as IKZF1, CDKN2A, and antigen receptor gene deletions in IGH or TRG2 can distinguish between de novo BCR-ABL + AML from myeloid blast crisis of CML [1,2]. Certain other reported clinical features in the literature can also guide in this diagnostic dilemma, as mentioned in the table: 2; however, they may not be seen in every case [5,6].
Our patient presented with clinical features of splenomegaly, peripheral circulating basophils more than 2% with blast cells, and hypercellular bone marrow supporting CML-BP diagnosis [6]. He had mixed cellular phenotypic variation of CML-BP and AML with monocytic differentiation on bone marrow examination, which created another differential diagnosis of de novo AML on the table. Later after discussing the case in an MDT of hemato-histopathologist and reviewing the patient’s clinical file supplemented with cytogenetics and molecular analysis, he was labeled as a case of CML-BP and treated accordingly with TKI therapy, i.e., dasatinib but did not respond adequately. Later T315I mutation analysis came positive, and he received the recommended treatment with ponatinib therapy with optimal response [3].
The reason to differentiate de novo AML is based upon its difference in genetic and molecular nature that poses high-risk other than BCR/ABL+ gene only, treatment modality, and response from CML [1,2,3,4]. Studies have also revealed that de novo AML with BCR/ABL has more prevalence of fusion protein 190 and NPM1 mutation in contrast to Ph+ CML and also possess different treatment and prognostic value than CML with BCR/ABL-1 in blast phase [7]. After a thorough literature search, we managed to execute a table to guide the CML-BP and de novo gene AML, table:2.
Although the myeloid blast phase is quite common, the monocytic blast phase of CML associated with T315I is the first case reported in our National Center for Cancer care and research institute (NCCCR) in Qatar.