BCR-ABL-positive acute myeloid leukemia: a new entity? Analysis of clinical and molecular features

Abstract

BCR-ABL-positive acute myeloid leukemia (AML) is a rare subtype of AML that is now included as a provisional entity in the 2016 revised WHO classification of myeloid malignancies. Since a clear distinction between de novo BCR-ABL+ AML and chronic myeloid leukemia (CML) blast crisis is challenging in many cases, the existence of de novo BCR-ABL+ AML has been a matter of debate for a long time. However, there is increasing evidence suggesting that BCR-ABL+ AML is in fact a distinct subgroup of AML. In this study, we analyzed all published cases since 1975 as well as cases from our institution in order to present common clinical and molecular features of this rare disease. Our analysis shows that BCR-ABL predominantly occurs in AML-NOS, CBF leukemia, and AML with myelodysplasia-related changes. The most common BCR-ABL transcripts (p190 and p210) are nearly equally distributed. Based on the analysis of published data, we provide a clinical algorithm for the initial differential diagnosis of BCR-ABL+ AML. The prognosis of BCR-ABL+ AML seems to depend on the cytogenetic and/or molecular background rather than on BCR-ABL itself. A therapy with tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib, or nilotinib is reasonable, but-due to a lack of systematic clinical data-their use cannot be routinely recommended in first-line therapy. Beyond first-line treatment of AML, the use of TKI remains an individual decision, both in combination with intensive chemotherapy and/or as a bridge to allogeneic stem cell transplantation. In each single case, potential benefits have to be weighed against potential risks.

“Chronic myelogenous leukemia in primary blast crisis” rather than “de novo BCR‐ABL1‐positive acute myeloid leukemia”

“…Consequently, the presence of the Philadelphia chromosome in less than 100% of metaphases during karyotype is the major criterion for the diagnosis of BCR‐ABL1 + AML . In our case, the presence of the Philadelphia chromosome in all the metaphases, the detection of p210 rather than p190 transcript, and the absence of AML driver mutations were all in favor of the diagnosis of CML‐BC . Moreover, trisomy 8 is the most frequent additional cytogenetic alterations observed during the evolution of CML, although it is uncommon in AML .…”

“…Thus, in our report, cytological examination is in favor of the diagnosis of CML‐BC rather than de novo BCR‐ABL1 AML. On the other hand, myelodysplastic changes are most often associated with de novo BCR‐ABL1 AML . However, in our case, the absence of cytogenetics abnormalities or mutations associated with myelodysplastic syndrome leads us to exclude the diagnosis of AML with myelodysplasia‐related changes.…”

Bone marrow core biopsy in 508 consecutive patients with chronic myeloid leukemia: Assessment of potential value

“…Patients with CML of any phase were included. Patients with BCR‐ABL1 –positive acute myeloid leukemia or mixed‐phenotype acute leukemia without a documented history of CML were excluded . Clinical information and BM morphology at the time of the initial diagnosis or first presentation to our institution were reviewed.…”

Myeloproliferative neoplasms: Diagnostic workup of the cythemic patient

“…Patients in the first category usually show prominent splenomegaly, carry mutations in growth factor signaling genes, and show generally good response to tyrosine kinase inhibition. In contrast, patients with de novo AML with BCR‐ABL1 lack splenomegaly and basophilia, show frequent aberrant expression of lymphoid markers, and respond poorly to tyrosine kinase inhibitors as well as standard AML therapy …”