University of Southampton, UK.
Br J Haematol. 2010 Jan;148(2):268-73. doi: 10.1111/j.1365-2141.2009.07955.x.
We identified four patients who presented with BCR-ABL1 negative myeloproliferative neoplasms and cytogenetically visible abnormalities of chromosome band 5q31-35. Fluorescence in situ hybridization indicated that the platelet-derived growth factor receptor beta gene (PDGFRB) was disrupted in all four cases and 5' rapid amplification of cDNA ends identified in-frame mRNA fusions between PDGFRB and WDR48 (3p21), GOLGA4 (3p21) and BIN2 (12q13). Strikingly, all three genes encode proteins involving intracellular trafficking. Imatinib, a known inhibitor of PDGFRbeta, selectively blocked the growth of t(3;5) myeloid colonies and produced clinically significant responses in all patients. We conclude that PDGFRB fuses to diverse partner genes in atypical myeloproliferative neoplasms (MPNs). Although very rare, identification of these fusions is critical for proper management of affected individuals.
我们发现了 4 名患者，他们表现出 BCR-ABL1 阴性骨髓增殖性肿瘤和染色体带 5q31-35 处可观察到的细胞遗传学异常。荧光原位杂交表明，所有 4 例患者的血小板衍生生长因子受体β基因（PDGFRB）均被破坏，5'快速扩增 cDNA 末端鉴定出 PDGFRB 与 WDR48（3p21）、GOLGA4（3p21）和 BIN2（12q13）之间的框内 mRNA 融合。引人注目的是，所有这三个基因编码的蛋白质都涉及细胞内运输。伊马替尼是一种已知的 PDGFRbeta 抑制剂，选择性地阻断了 t(3;5)髓系集落的生长，并使所有患者均产生了具有临床意义的反应。我们得出结论，PDGFRB 在非典型骨髓增殖性肿瘤（MPN）中与不同的伙伴基因融合。尽管非常罕见，但这些融合的鉴定对于受影响个体的正确管理至关重要。
