TY - JOUR
T1 - Myeloid neoplasms with concurrent BCR-ABL1 and CBFB rearrangements
T2 - A series of 10 cases of a clinically aggressive neoplasm
AU - Salem, Alireza
AU - Loghavi, Sanam
AU - Tang, Guilin
AU - Huh, Yang O.
AU - Jabbour, Elias J.
AU - Kantarjian, Hagop
AU - Wang, Wei
AU - Hu, Shimin
AU - Luthra, Rajyalakshmi
AU - Medeiros, L. Jeffrey
AU - Khoury, Joseph D.
N1 - Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2017/6
Y1 - 2017/6
N2 - 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 six men and four women with a median age of 51 years (range, 20-71 years). The sequence of molecular alterations could be determined in nine cases: BCR-ABL1 preceded CBFB rearrangement in seven, CBFB rearrangement preceded BCR-ABL1 in one, and both alterations were discovered simultaneously in one 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 three cases. Two patients were treated with the FLAG-IDA regimen (fludarabine, cytarabine, idarubicin, and G-CSF) and tyrosine kinase inhibitors (TKI); seven 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.
AB - 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 six men and four women with a median age of 51 years (range, 20-71 years). The sequence of molecular alterations could be determined in nine cases: BCR-ABL1 preceded CBFB rearrangement in seven, CBFB rearrangement preceded BCR-ABL1 in one, and both alterations were discovered simultaneously in one 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 three cases. Two patients were treated with the FLAG-IDA regimen (fludarabine, cytarabine, idarubicin, and G-CSF) and tyrosine kinase inhibitors (TKI); seven 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.
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U2 - 10.1002/ajh.24710
DO - 10.1002/ajh.24710
M3 - Article
C2 - 28253536
AN - SCOPUS:85017381163
SN - 0361-8609
VL - 92
SP - 520
EP - 528
JO - American journal of hematology
JF - American journal of hematology
IS - 6
ER -