title: Myeloid neoplasms with concurrent BCR-ABL1 and CBFB rearrangements: A series of 10 cases of a clinically aggressive neoplasm.
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 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.
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Alireza
authors.identifier: http://orcid.org/0000-0001-5492-1962
authors.initials: A
authors.lastname: Salem
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Sanam
authors.initials: S
authors.lastname: Loghavi
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Guilin
authors.initials: G
authors.lastname: Tang
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Yang O
authors.initials: YO
authors.lastname: Huh
authors.affiliation: Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Elias J
authors.identifier: http://orcid.org/0000-0003-4465-6119
authors.initials: EJ
authors.lastname: Jabbour
authors.affiliation: Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Hagop
authors.identifier: http://orcid.org/0000-0002-1908-3307
authors.initials: H
authors.lastname: Kantarjian
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Shimin
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Rajyalakshmi
authors.initials: R
authors.lastname: Luthra
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Khoury
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D003131:Combined Modality Therapy; D050658:Core Binding Factor beta Subunit / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D012189:Retrospective Studies; D014178:Translocation, Genetic; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D050658:Core Binding Factor beta Subunit; D016044:Fusion Proteins, bcr-abl