A study on the incidence of ABL gene deletion on derivative chromosome 9 in chronic myelogenous leukemia by interphase fluorescence in situ hybridization and its association with disease progression

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Abstract
Fluorescence in situ hybridization for the BCR/ABL rearrangement in 138 bone marrow specimens from 59 Philadelphia+ (Ph+) chronic myelogenous leukemia (CML) patients, 35 Ph+ acute lymphoblastic leukemia (ALL) patients, and 57 Ph− ALL patients was used. Sixteen (27.1%) of the 59 CML patients had deletions of the residual ABL gene on the derivative chromosome 9. During the study period, 32 of the 59 CML patients progressed to blast crisis or accelerated phase. Of these, nine patients had residual ABL gene deletions on the derivative chromosomes 9 and 23 patients had no deletions. The mean duration from first diagnosis to blast crisis or accelerated phase for the nine patients with ABL deletions was 32.8 months, and for the 23 patients without ABL deletions, it was 62.4 months (P = 0.017). The overall survival time for the 16 patients with deletions was 32.8 months, and for the 43 patients without deletions, it was 60.1 months (P = 0.164). ABL deletions were not detected among the 35 ALL patients (17 with major BCR/ABL, 18 with minor BCR/ABL), and it appears that this deletion occurs rarely or not at all in Ph+ ALL patients, which is in contrast to the CML patients (27.1%). However, we detected two ALL cases with ABL deletion but without BCR/ABL rearrangement among 49 Ph− ALL and 66 Ph− AML patients. In conclusion, patients with ABL deletions progress to blast crisis or accelerated phase in a significantly shorter time than do those without such deletions. It is therefore suggested that the ABL deletion is an indicator of a poor prognosis in CML.