摘要
为了探讨FLT3基因及FLT3内部串联重复(ITD)突变与恶性血液病的关系及临床意义,采用PCR结合DNA测序技术分析32例急性髓系白血病(AML)、18例急性淋巴细胞白血病(ALL)、2例急性杂合性白血病(AHL)、12例骨髓增生异常综合征(MDS)、10例慢性粒细胞白血病(CML)、3例非何杰金淋巴瘤(NHL)及9例多发性骨髓瘤(MM)患者骨髓单个核细胞中FLT3基因及FLT3/ITD突变,分析FLT3/ITD阳性患者的临床特征及疗效。结果表明:在32例AML患者中5例FLT3/ITD(15.6%)阳性,其中7例M3中1例、10例M4中1例、10例M5中3例;而在18例ALL、2例AHL、12例MDS和10例CML患者中未检测到FLT3/ITD突变;在3例非何杰金淋巴瘤(NHL)、9例多发性骨髓瘤(MM)患者中亦未检测到FLT3基因。对2例特征性突变进行了测序,其结果显示,ITD位于外显子14,长度为27-63bp,为单纯串联重复,FLT3/ITD序列包括有2个SH2-结合结构域(YEYV与YEYDLK),其中1例出现氨基酸的替换,其ITD序列及氨基酸的替换均具有独特性,均未改变FLT3阅读框架。临床研究表明,FLT3/ITD阳性AML患者外周血白细胞数高(p<0.01),骨髓原始细胞比例高(p<0.01),化疗后有低缓解率趋势。结论:FLT3/ITD突变多见于M5患者,为框内突变。FLT3/ITD阳性的AML患者外周血白细胞数高,骨髓原始细胞比例高,伴低缓解率趋势。FLT3/ITD基因突变可作为预测AML预后的一个指标。
To study the FLT3 gene expression and its internal tandem duplication in hematologic malignancies and its clinical significance, polymerase chain reaction （PCR） and DNA sequencing were used to detect the FLT3/ITD mutation in blast cells of bone marrow from 86 patients with hematologic malignancies, including 32 cases of acute myeoloid leukemia （AML）, 18 cases of acute lymphoblastic leukemia （ALL）, 2 cases of acute hybrid leukemia （AHL） , 12 cases of myelodysplastic syndromes （MDS） , 10 cases of chronic myelogenous leukemia （CML）, 3 cases of non-Hodgkin＇s lymphoma （NHL） and 9 cases of multiple myeloma （MM）. The resultes showed that the expression of FLT3 / ITD gene could be detected in 5 of 32 （ 15.6% ） AML patients, including 1/7 of M3 , 1/10 of M4 and 3/10 of Ms. More FLT3 aberrations were found in AML- M5. No FLT3/ITD was found in 18 cases of ALL, in 2 cases of AHL, in 12 cases of MDS and in 10 cases of CML. No FLT3 was found in 3 cases of NHL and in 9 cases of MM. Sequence analysis in 2 case with abnormal PCR electrophoretic patterns revealed that the ITDs were located within exon 14 from 27 to 63 bp, which was a simple tandem duplication, and did not altered the reading frame. FLT3/ITD was associated with a higher peripheral blood white cell count （p 〈0.01 ）, higher percentage of bone marrow blast cells （p 〈 0.01 ） and lower complete mission rate. It is concluded that more FLT3/ITD mutation occurs in AML-M5 patients. Sequence of the mutants is in frame mutation. FLT3/ITD mutation is associated with higher peripheral blood white cell count, higher percentage of bone marrow blast cells and lower complete remission rate, FIT3/IID gene mutation may be used to predict prognosis of patients with AML.
出处
《中国实验血液学杂志》
CAS
CSCD
2007年第4期709-713,共5页
Journal of Experimental Hematology
