应用荧光原位杂交技术诊断成人Ph样急性淋巴细胞白血病

OBJECTIVE: To establish a screening system of adult Philadelphia chromosome-like acute lymphoblastic leukemia（Ph-like ALL）by fluorescence in situ hybridization（FISH）. METHODS: Based on the genetic characteristics of Ph-like ALL, FISH probes were designed for ABL1, ABL2, JAK2, EPOR, CRLF2, CSF1R, PDGFRB, and P2RY8 gene breakpoints, which were used to screen Ph-like ALL in B-ALL patients without BCR-ABL1, ETV6-RUNX1, MLL, and E2A gene arrangement. Furthermore, it was analyzed in combination with flow immunophenotype, next-generation sequencing for targeted gene mutations, and RNA sequencing（RNA-seq）. RESULTS: A total of 189 adult B-ALL patients diagnosed in Nanfang Hospital from January 2016 to April 2019 were enrolled in this study. Using FISH and/or PCR, BCR-ABL1, ETV6-RUNX1, MLL, or E2A arrangement was detected in 83 of them, and Ph-like ALL was detected by FISH in the other 106, resulting in the presence of typical gene arrangements of Ph-like ALL in 12 patients（11.3％, 12/106）. Validated by RNA-seq, the sensitivity and specificity of FISH for Ph-like ALL were 71.4％ and 95.8％, respectively. After further analysis with immunophenotype, targeted gene mutations, and RNA-seq, 14（13.2％, 14/106）were diagnosed with Ph-like ALL. CONCLUSION: This data shows high specificity of FISH for identification of Ph-like ALL and combining immunophenotype and sequencing technology can improve the diagnostic system.