title: Coexistence of different clonal populations harboring the b3a2 (p210) and e1a2 (p190) BCR-ABL1 fusion transcripts in chronic myelogenous leukemia resistant to imatinib.
abstract: In this study, we report the case of a Philadelphia (Ph) positive chronic myelogenous leukemia (CML) patient with the presence of p190 and p210 BCR-ABL1 mRNA fusion transcripts derived from e1a2 and b3a2 BCR-ABL1 genomic rearrangements, respectively. The presence of e1a2 BCR-ABL1 genomic rearrangement was seen in 2 different clones, one with the rearrangement and another one with the rearrangement and deletion of the BCR gene of the non-rearranged chromosome 22. After treatment with imatinib, the p210 transcript could not be detected, whereas p190 was still present 6 months after initiation of imatinib therapy and progression to blast phase. The absence of p210 transcript post treatment indicates that the clone with b3a2 responded to imatinib and that the observed resistance was associated to cells harboring the e1a2 genomic rearrangement. Despite resistance of this patient to imatinib, no evidence of mutations in the kinase domain of ABL1 was found. Loss of normal BCR in one cell clone may contribute to the resistance to imatinib due to the lack of BCR mediated inhibition of BCR-ABL1.
authors.affiliation: Area of Cancer, Area of Cell Therapy and Hematology Service, University Clinic, University of Navarra and Foundation for Applied Medical Research, Avda. Pio XII 36, Pamplona, Spain.
authors.forename: Xabier
authors.initials: X
authors.lastname: Agirre
authors.forename: José
authors.initials: J
authors.lastname: Román-Gómez
authors.forename: Iria
authors.initials: I
authors.lastname: Vázquez
authors.forename: Antonio
authors.initials: A
authors.lastname: Jiménez-Velasco
authors.forename: María J
authors.initials: MJ
authors.lastname: Larráyoz
authors.forename: Idoya
authors.initials: I
authors.lastname: Lahortiga
authors.forename: Enrique J
authors.initials: EJ
authors.lastname: Andreu
authors.forename: José
authors.initials: J
authors.lastname: Márquez
authors.forename: José M
authors.initials: JM
authors.lastname: Beltrán de Heredia
authors.forename: María D
authors.initials: MD
authors.lastname: Odero
authors.forename: Felipe
authors.initials: F
authors.lastname: Prósper
authors.forename: María J
authors.initials: MJ
authors.lastname: Calasanz
mesh_terms: D000368:Aged; D001549:Benzamides; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D015321:Gene Rearrangement; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics*; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis*
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl