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1p21 deletions are strongly associated with 1q21 gains and are an independent adverse prognostic factor for the outcome of high-dose chemotherapy in patients with multiple myeloma.

Research paper by H H Chang, X X Qi, A A Jiang, W W Xu, T T Young, D D Reece

Indexed on: 19 May '09Published on: 19 May '09Published in: Bone Marrow Transplantation



Abstract

Deletions involving chromosome 1p are frequent events in multiple myeloma (MM). As karyotyping and single nucleotide polymorphism-based mapping analysis identify a minimal common deletion region involving the 1p21 locus, we investigated the prevalence and prognostic significance of del(1p21) in 203 MM patients undergoing high-dose therapy and autologous SCT. 1p21 status was also evaluated in 16 patients with monoclonal gammopathy of undetermined significance (MGUS) and 41 patients with plasma cell leukemia (PCL). FISH combined with cytoplasmic light chain detection (cIg-FISH) detected hemizygous 1p21 deletions in 18% of the MM, 34% of PCL but none of the MGUS cases. The presence of 1p21 deletions was correlated with 1q21(CKS1B) amplification (P=0.01), and del17p(TP53) (P=0.05) but not with del(13q), t(11;14) or t(4;14). Patients with 1p21 deletions had significantly shorter progression-free survival (PFS; median 14.2 vs 25.4 months, P<0.001) and overall survival (OS; median 39.4 vs 82.3 months, P=0.001) than those without such deletions. In multivariate analysis, del(1p21) was an independent risk factor for PFS (P= 0.003) and OS (P=0.013) after adjusting for del(13q), del(p53), t(4;14) and 1q21 amplifications. Our results indicate that del(1p21) is an independent poor prognostic factor associated with disease progression in MM.