The role of the SNF5 gene in the progression of chronic myelocytic leukemia

一些证据表明，肿瘤抑制基因的失活与多种人类肿瘤的发生密切相关。这种失活通常是由一个等位基因的突变伴随着第二个等位基因的丢失引起的。为了解慢性粒细胞白血病（CML）急变期（BC）的遗传学改变，我们分析了22号染色体长臂（22 q）SNF 5基因的异常。细胞遗传学分析发现184例血液肿瘤患者22号染色体异常。122例CML患者均存在t（9 ; 22）（q34 ; q11）。在122例患者中，2例有22 q-以及t（9 ; 22）（q34 ; q11）。1例骨髓增生异常综合征（MDS）患者的SNF 5基因-22和22 q-均缺失，我们用微卫星标记检测了30例CML患者从慢性期进展到BC过程中22 q的等位基因缺失。我们在18例CML BC患者中的2例中检测到22 q的杂合性丢失（洛）。我们还检查了24例从MDS进展为急性髓细胞白血病（AML）的患者的22 q等位基因丢失。在1例由MDS演变而来的AML患者中发现22 q的等位基因丢失，在CML BC和其他血液肿瘤中发现22和22 q-，我们对SNF 5基因进行了PCR-SSCP分析以检测微小突变。我们发现1例SNF 5基因迁移率改变，但序列分析显示多态性，由于1例MDS患者出现-22和22 q-，我们正在进行SNF 5基因的FISH分析。单倍性不足可能促进血液肿瘤（包括CML）的进展。

Several lines of evidence have shown that inactivation of tumor suppressor genes is closely associated with tumorigenesis in a wide variety of human tumors. Such inactivation is often caused by a mutation of one allele accompanied by loss of the second allele. To know genetic changes in blast crisis (BC) of chronic myelocytic leukemia (CML), we analyzed abnormalities of the SNF5 gene on long arm of chromosome 22 (22q). Cytogenetic analysis revealed abnormalities of chromosome 22 in 184 patients with hematologic neoplasms. All 122 patients with CML had t(9 ; 22)(q34 ; q11). Of the 122 patients, two had 22q- as well as t(9 ; 22)(q34 ; q11). One patient with myelodysplastic syndrome (MDS) showed -22 and 22q-, suggesting that both alleles of the SNF5 gene were deleted.We examined 22q for allelic loss in the progression of CML, using microsatellite markers in 30 patients who progressed from chronic phase to BC. We detected loss of heterozygosity (LOH) on 22q in two of 18 patients with CML BC. We also examined allelic loss on 22q in 24 patients who progressed from MDS to acute myeloblastic leukemia (AML). Allelic loss was observed on 22q in one case of AML that had evolved from MDS.In CML BC and other hematologic neoplasms showing 22 and 22q-, we performed PCR-SSCP analysis on the SNF5 gene to detect subtle mutations. We found mobility shifts inone case, however sequence analysis showed polymorphism.Since one patient with MDS showed -22 and 22q-, FISH analysis on the SNF5 gene is now underway. Haplo in sufficiency may contribute to the progression of hematologic neoplasms including CML.