BCR-ABL + acute myeloid leukemia: are we always dealing with a high-risk disease?

Abstract

BCR-ABL 1 acute myeloid leukemia (AML) has recently been listed in the 2016 revised World Health Organization (WHO) classification of myeloid malignancies as a provisional entity. 1 BCR-ABL 1 AML comprises a group of de novo AML in patients without evidence of an underlying chronic myeloid leukemia (CML) and without cooccurring aberrations such as CEBPA, NPM1, inv(16), and inv(3) that would lead to the classification as "AML with recurrent genetic aberrations." Although there is some overlap between BCR-ABL 1 AML, myeloid CML blast crisis, and BCR-ABL 1 mixed phenotype acute leukemia, no definite criteria have yet been defined to distinguish among these entities. However, a loss of IKZF1 and CDKN2A as well as cryptic deletions in IGH and TRG genes have recently been reported in BCR-ABL 1 AML and seem to be absent in myeloid blast crisis of CML. Therefore, these additional molecular markers may be helpful for differential diagnosis in clinically difficult situations. 2

Association of Chronic Myelogenous (Basophilic) Leukemia and the BCR/ABL Mutation in a Yucatan Barrow (Sus scrofa domestica)

“…As mentioned previously, the presence of the Philadelphia gene is a hallmark of CML and only a rare subset of acute myeloid leukemias (AML) (30,31). The barrow in this report appeared to display the standard stages of CML including a relatively insidious disease onset with a chronic phase in which symptoms waxed and waned followed by what might be considered a rapid or accelerated phase that progressed to a fatal blast crisis.…”

An interesting case of chronic myeloid leukemia (CML) with T315I mutation raising suspicion of de novo AML, a diagnostic conundrum.

“…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].…”

“…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].…”

“…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].…”

Sustained Complete Remission with Incomplete Hematologic Recovery (CRi) in a Patient with Relapsed AML and Concurrent BCR-ABL1 and CBFB Rearrangement Treated with a Combination of Venetoclax and 5-Azacytidine

“…The co-occurrence of BCR-ABL1 fusion and core-binding factor (CBF) rearrangement, particularly CBFB-MYH11 fusion, resulting from inv(16)(p13.1q22) or less commonly t(16;16)(p13.1;q22), is extremely rare, and its clinical significance remains largely unknown [3-5]. Unlike de novo AML with only CBFB rearrangement, the coexistence of BCR-ABL1 fusion and CBFB rearrangement is associated with poor clinical outcome, suggesting that high-intensity chemotherapy, possibly associated with tyrosine kinase inhibitors (TKIs), is a reasonable option [6, 7]. Herein, we describe the clinical outcome of an AML patient harboring BCR-ABL1 fusion and CBFB rearrangement refractory to intensive chemotherapy and different TKIs who achieved sustained complete remission with incomplete hematologic recovery (CRi) after therapy of combination with venetoclax and 5-azacytidine.…”