急性淋巴细胞白血病高危亚型的精确诊断与个体化治疗.pdf

葛峥 教授 主任医师 东南大学附属中大医院 江苏省医学重点人才 国家自然科学基金评审专家 国中西医结合学会血液专委会全国委员 中华医学会江苏省血液专委会白血病学组委员 江苏省免疫学会血液免疫专委会委员 美国血液学会会员 欧洲血液学会会员 研究方向：急性白血病的临床诊治和基础研究 承担课题：国家自然科学基金面上项目等科研项目 急性淋巴细胞白血病的高危亚型 精准诊断和个体化治疗 葛 峥 东南大学附属中大医院血液科 Genetic subtypes of ALL • High hyperdiploidy （高二倍体）with 50 chromosomes • Hypodiploidy(低二倍体）with 44 chromosomes Chromosomal rearrangements: • t(12;21)(p13;q22) ETV6-RUNX1 (TEL-AML1) • t(1;19)(q23;p13) TCF3-PBX1 (E2A-PBX1) • t(9;22)(q34;q11) BCR-ABL1 • rearrangements of MLL • rearrangement of CRLF2 • Ph-like ALL • ERG ALL • T-lineage ALL (ETP ALL) Ph-like ALL Ph-like ALL 特征 BCR-ABL1 negative, but exhibit a gene expression profile similar to that of BCR-ABL1-positive ALL. pink bars red bars Ph-like ALL 特征 Ph-like ALL have alteration of B-lymphoid transcription factor genes (most commnoly IKZF1). Ph-like ALL are associated with poor outcome. With an increasing prevalence with increasing age. Diverse range of kinase-activating rearrangements and mutations. Genetic subtypes of Ph-like ALL Breakdown of Ph-like ALL into: CRLF2-rearranged JAK mutant CRLF2-rearranged JAK WT other kinase lesions unknown Genetic subtypes of Ph-like ALL Breakdown of “other kinase lesion” into: Breakdown of Ph-like ALL into: ABL1-class CRLF2-rearranged JAK mutant (ABL1, ABL2, CSF1R, PDGFRB) CRLF2-rearranged JAK WT JAK2 rearrangements other kinase lesions Other JAK-STAT unknown (FLT3,I