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.