SUBCLASSFICIATION OF MULTIPLE MYELOMA BASED ON THE PARTNER GENES OF TUMOR-SPECIFIC IMMUNOGLOBULIN HEAVY CHAIN GENE TRANSLOCATION BY USING DOUBLE-COLOR FLUORESCENCE IN SITU HYBRIDIZATION

染色体易位涉及免疫球蛋白重链（IGH）基因在带14q32.3和它的伙伴基因的发病机制和B细胞恶性肿瘤的临床特征。为了明确14q32.3易位与特定癌基因位点的发生率，我们分析了113例MM患者的双色荧光原位杂交（DC-FISH）。使用IGH基因（14q32.3）与c-MYC（8q24.1）、CCND 1（11q13.3）、FGFR 3（4p 15）、MUM 1/IRF 4（6p 25）和BCL 2（18 q21）基因探针的组合，在105名通过DC-FISH评估的患者中的69名（66%）中检测到IGH易位。染色体t（11 ;在38名患者中的27名（71%）中检测到t（8 ; 14）作为CCND 1与IGH探针的融合信号;在35名患者中的11名（31%）中检测到t（8 ; 14）作为c-MYC与IGH的融合;并且在38名患者中的8名（21%）中检测到t（6 ; 14）作为MUM 1与IGH的融合。IGH双易位9例（21%）. CCND 1/IGH重排与MM的浆细胞白血病或白血病表现有关。 ...更多信息 与侵袭性疾病相关。FGFR 3/IGH重排患者常出现溶骨性病变，根据其表面免疫表型可分为前B细胞（CD 38+，CD 19-）、未成熟浆细胞（CD 38+，CD 19-，MPC-）和成熟浆细胞（CD 38+，CD 19-，MPC+）。在所有15例分析的患者中，前B细胞均未参与IGH易位。我们根据携带IGH易位的细胞群体定义了三种不同的模式：未成熟（-）和成熟（+），未成熟（+）和成熟（+），以及未成熟（-f）和成熟（-）。FGFR阳性患者表现出所有三种模式，而c-MYC或CCND 1阳性患者未表现出不成熟（+）/成熟（-）模式。目前的研究表明，单个IGH易位可以将正常细胞转化为骨髓瘤细胞，并且FGFR 3/IGH易位在骨髓瘤发生过程中既作为原发事件也作为附加事件发生。此外，c-MYC/IGH或FGFR 3/IGH易位的获得可能与疾病的进展相关。少

Chromosomal translocation involving the immunoglobulin heavy chain (IGH) gene at band 14q32.3 and its partner genes are implicated in both the pathogenesis and clinical characteristics of B-cell malignancies. To define the incidence of 14q32.3 translocation with specific oncogene loci, we analyzed 113 patients with MM by double-color fluorescence in situ hybridization (DC-FISH). Using the IGH gene (14q32.3) in combination with c-MYC (8q24.1), CCND1 (11q13.3), FGFR3 (4p15), MUM1/IRF4(6p25), and BCL2 (18q21) gene probes detected IGH translocations in 69 (66 %) of 105 patients who were assessed by DC-FISH. Chromosome t(11 ; 14) was detected in 27 (71 %) of 38 patients as fusion signal of CCND1 with IGH probes; t(8 ; 14) in 11 (31 %) of 35 as fusion of c-MYC with IGH ; and t(6 ; 14) in 8 (21 %) of 38 as MUM1 with IGH. Double IGH translocation was detected 9 (21 %) of 43 patients. CCND1/IGH rearrangement was associated with plasma cell leukemia or leukemia manifestation of MM. C-MYC/IGH rea … More rrangement was associated with aggressive disease. Lytic bone lesion was frequently found in patients with FGFR3/IGH rearrangement.Three distinct cell populations were defined based on the surface immunophenotype ; pre-B cell (CD38+, CD19-), immature plasma cell (CD38+, CD19-, MPC-), and mature plasma cell (CD38+, CD19-, MPC+). Pre-B cells were not involved in IGH translocation in all 1 5 patients analyzed. We defined three distinct patterns based on cell populations carrying IGH translocation; immature(-) and mature(+), immature(+) and mature(+) , and immature(-f) and mature(-). FGFRS-positive patients demonstrated all three patterns, whereas c-MYC- or CCND1-positive patients did not showed immature(+)/mature(-) pattern. The present studies suggest that single IGH translocation can transform normal cells to myeloma cells and that FGFR3/IGH translocation occurs as both primary and additional event during the myelomagenesis. Furthermore, acquisition of c-MYC/IGH or FGFR3/IGH translocation may be associated with progression of the diseases. Less