A Novel Recurrent Chromosomal Inversion, Inversion(9)(p21q34), in Ph-Positive Leukemia Patients.

Abstract 4242

A pericentric inversion(9)(p21q34) was identified in five Ph-positive leukemia patients including four patients with chronic myeloid leukemia(CML) in chronic phase(CP) and one patient with acute myeloid leukemia (AML) since 1998. Among them, two were males, three wrer females. The median age is 31 years (range 21-52 years). Conventional karyotypic analysis with R-banding technique showed that the inv(9)(p21q34) always occurred in the der(9)t(9;22)(q34;q11) and was accompanied by the der(22)t(9;22)(q34;q11) in all metaphases analyzed in four patients with CML-CP at diagnosis. One patient with AML presented three clones: one with normal karyotype, one with sole t(9;22)(q34;q11), one with inv(9)(p21q34) involving the der(9)t(9;22) and additional t(8;12)(q12;p11). FISH using LSI BCR/ABL dual-color, dual fusion probe, chromosome painting(CP) with the paint probes for chromosome 9p and 9q and RT-PCR using the primers of the BCR/ABL fusion genes were performed in four of them. FISH showed the coexistence of clone with sole t(9;22) and another with inv(9)(p11q34) and t(9;22) in four patients in whom, one patient also showed a deletion of partial sequence from BCR on der(9)t(9;22)inv(9)(p21q34). RT-PCR revealed a b3a2 transcript for BCR/ABL fusion gene transcript. FISH proved that the inv(9)(p21q34) disrupted the ABL/BCR fusion gene at the molecular level. However, it does not appear to have any biological significance because BCR/ABL fusion gene is thought to be involved in the pathogenesis of CML, while ABL/BCR fusion gene is merely mechanical consequence of the t(9;22) translocation. As far as we know, inv(9)(p21q34) has not been reperted previously. Thus, it should be regarded as a novel rare but recurrent secondary chromosomal anomaly. In this series, one lost to follow-up, one patient transformed into B cell acute lymphocytic leukemia, who and other two patients survivals of 28 days, 13 and 34 months, respectively. Only one remains alive. Their dismal outcome probably suggests inv(9)(p21q34) having unfavourable impact on prognosis. At present, no firm conclusion can be drawn from this study. More patients with this anomaly need to be investigated to elucidate its prognostic significance.