Myeloid Neoplasms with Concurrent BCR-ABL1 and CBFB Rearrangements: A Series of 10 Cases of a Clinically Aggressive Neoplasm.

Myeloid Neoplasms with Concurrent BCR-ABL1 and CBFB Rearrangements: A Series of 10 Cases of a Clinically Aggressive Neoplasm.

Am J Hematol. 2017 Mar 02;:

Authors: Salem A, Loghavi S, Tang G, Huh YO, Jabbour EJ, Kantarjian H, Wang W, Hu S, Luthra R, Medeiros LJ, Khoury JD

Abstract
Chronic myeloid leukemia (CML) is defined by the presence of t(9;22)(q34;q11.2)/BCR-ABL1. Additional chromosomal abnormalities confer an adverse prognosis and are particularly common in the blast phase of CML (CML-BP). CBFB rearrangement, particularly CBFB-MYH11 fusion resulting from inv(16)(p13.1q22) or t(16;16)(p13.1;q22), is an acute myeloid leukemia (AML)-defining alteration that is associated with a favorable outcome. The co-occurrence of BCR-ABL1 and CBFB rearrangement is extremely rare, and the significance of this finding remains unclear. We identified 10 patients with myeloid neoplasms harboring BCR-ABL1 and CBFB rearrangement. The study group included 6 men and 4 women with a median age of 51 years (range, 20-71 years). The sequence of molecular alterations could be determined in 9 cases: BCR-ABL1 preceded CBFB rearrangement in 7, CBFB rearrangement preceded BCR-ABL1 in 2, and both alterations were discovered simultaneously in 1 patient. BCR-ABL1 encoded for p210 kD in all cases in which BCR-ABL1 preceded CBFB rearrangement; a p190 kD was identified in the other 3 cases. Two patients were treated with the FLAG-IDA regimen (fludarabine, cytarabine, idarubicin and G-CSF) and tyrosine kinase inhibitors (TKI); 7 with other cytarabine-based regimens and TKIs, and one with ponatinib alone. At last follow up (median, 16 months; range 2-85), 7 of 10 patients had died. The co-existence of BCR-ABL1 and CBFB rearrangement is associated with poor outcome and a clinical course similar to that of CML-BP, and unlike de novo AML with CBFB rearrangement, suggesting that high-intensity chemotherapy with TKI should be considered in these patients. This article is protected by copyright. All rights reserved.

PMID: 28253536 [PubMed - as supplied by publisher]

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