36例11q23/Mll融合基因白血病的分子生物学和临床特点分析

本研究分析急性白血病(AL)伴11q23/mll融合基因阳性的患者临床和分子生物学特点,探讨适宜的治疗策略。对36例急性白血病伴mll融合基因阳性患者的骨髓和外周血细胞形态学、免疫学、分子生物学、染色体特征以及患者治疗、生存情况进行总结分析。结果表明,在494例急性白血病患者中,mll融合基因阳性共36例,占7.2%,其中32例为急性髓细胞白血病(AML),免疫表型均为髓系表达,有5例同时伴淋系表达;4例为急性淋巴细胞白血病(ALL),免疫表型为B淋巴系表达,有3例同时伴有非系别确定性髓系标志表达。36例患者中29例(80%)可检测到克隆性染色体异常,其中有22例检测到11号染色体改变。对所有患者均进行了化疗,总缓解率为47.2%,25例缓解后的病人有10例在6个月内复发,其复发率为40%,有9例进行了异基因造血干细胞移植,其中7例移植后存活;共死亡24例。36例患者的中位生存期为16(2-46)个月,2年总生存率(OS)为41.4%,9例移植病人2年OS为87.5%。结论:白血病伴mll融合基因阳性的患者化疗效果差,易复发,预后差,异基因造血干细胞移植可明显改善MLL融合基因阳性AL患者的生存。

Clinical and Molecular Biologic Characteristics of 36 Cases of Leukemia with 11q23/Mll

This study was aimed to analyze the clinical and cytogenetic characteristics of acute leukemia with 11q23/mll rearrangement and explore the reasonable therapeutic principles. Characteristics in general situation, morphology, immunology, molecular biology, cytogenetics, treatment and overall survival of 36 cases of acute leukemias with mll gene rearrangement were studied and analyzed. The results showed that 36 cases with mll gene rearrangement were found positive（7.2%） in 494 patients with acute leukemia. Among the 36 cases of mll rearrangement positive, 32 cases were diagnosed as acute myeloid leukemia （AML） with myeloid antigen expression, of which 5 cases expressed lymphoblastic differentiation antigen; 4 cases were classified as B-lineage acute lymphoblastic leukemia（ALL）, of which non-lineage myeloid expression pattern were found in 3 cases. In 29 out of 36 cases （80%） the clonal chromosomal aberration were detected, of which chromosome 11 aberration were observed in 22 cases. All patients received chemotherapy with a total response rate of 47.2%. Of the responded patients, 10 cases relapsed within 6 months, with a recurrence rate of 40%;9 cases received hematopoietic stem cell transplantation （HSCT）, 7 cases of which survived after transplantation. The median survival time of 36 cases was 16 months（range 2-46） and their 2-year overall survival rate was 41.4%. The 2-year overall survival rate of 9 patients who received HSCT was 87.5%. It is concluded that acute leukemia patients with mll gene rearrangement show poor response to chemotherapy, high recurrence rate and poor prognosis. Hematopoietic stem cell transplantation may be a reasonable treatment principle to improve these patients＇ survival situation.