Cytogenetic,Molecular Genetic And Literature Review Of 2 Cases With Atypical T(15;17) Acute Promyelocytic Leukemia

Objective: To investigate the cytogenetic and molecular genetic characteristics of two patients with atypical t(15;17)acute promyelocytic leukemia(APL),and review the relative literature.Methods: The medical history,blood routine,coagulation function,bone marrow cell morphology,bone marrow immunotyping,and other clinical data of the two patients were collected,and the PML-RARα fusion gene was detected by chromosome karyotype analysis,fluorescence in situ hybridization(FISH)test,reverse transcription-polymerase chain reaction(RT-PCR),and the amplified products being Sanger sequenced.Furthermore,the common mutation genes of leukemia were checked in patient 1,and the transcriptome sequencing analysis was performed in patient 2.The clinical data of 27 cases of ins(17;15)insertion translocation and 53 cases of complex variant translocation in acute promyelocytic leukemia reported at home and abroad were summarized and analyzed.Results: Hemorrhage was the main clinical manifestation,and both the cell morphology and immunotyping of bone marrow showed typical APL characteristics in both patients.Chromosome karyotype analysis of patient 1 showed 48,XY,+8,+ mar,without t(15;17).The interphase FISH results suggested atypical signal characteristics of 2 red,1 green,1 yellow,and the metaphase FISH results suggested that the yellow fusion signal was located on chromosome 17 and the karyotype was 48,XY,+8,+mar,ins(17;15)(q21;q21q22).The RT-PCR and Sanger sequencing showed positive PMLRARα fusion gene,and the transcript type was S type.Genetic testing for common mutations in leukemia suggests a low frequency of FIT3-ITD mutations.Chromosome karyotype analysis of patient 2 was 45,XX,der(9)t(9;22)(p22;q13),t(15;22;17)(q22;q13;q21),-22.The FISH results showed atypical signal characteristics of 2 red,2 green,1 yellow.The RT-PCR and Sanger sequencing showed positive PMLRARα fusion gene,and the transcript type was L type.Transcriptome sequencing and analysis revealed that the patient carried the PML-RARα fusion gene and the RARα-SYN3 fusion gene.Both patients achieved complete remission(CR)after combined induction with all-trans-retinoic acid(ATRA)and arsenic trioxide(ATO).And distinguishingly,Patient 1 received 3 courses of IA regimen(idarubicin(IDA)+ cytarabine(Ara-C))consolidation therapy,followed by alternating maintenance therapy with ATRA and ATO.And Patient 2 underwent consolidation therapy with ATRA+ ATO,followed by alternating maintenance therapy with ATRA and ATO.Following up on March 2022,both patients were in continuous remission.The occult ins(17;15)APL patients have obvious curative effect on the combined induction therapy of ATRA and ATO.The proportion of transcript types in patients with ins(17;15)APL is close to that in patients with typical translocations.The ins(17;15)APL patients have a higher proportion of additional chromosomal abnormalities,but have no effect on their prognosis.The ratio of male to female with complex variant translocation APL was 1.1:1,and the median age was 44.5 years old(10-78 years old),and there was no significant difference in age and gender characteristics with the typical translocation APL patients.APL patients with complex variant translocations have a higher proportion of PMLRARα fusion genotype L-type transcripts,and the proportion of low-risk groups is higher.Complex variant translocations of APL can involve all chromosomes except chromosome 14 and Y chromosome,1p36,2q21,3p21,4q21,6p21,11q13,19p13,20p13,22q11.2,Xq13,the breakpoints appeared repeatedly and were reported at least twice.Conclusion: 1.APL with ins(17;15)insertion translocation is rare in the clinic.When the chromosome is normal but the PML-RARα fusion gene is positive,FISH probes with relatively large coverage should be selected for interphase FISH detection and combined with metaphase FISH to verify the translocation results.2.For APL with complex variant translocation,FISH detection and transcriptome sequencing can help to speculate the chromosomal translocation mechanism of complex translocation.3.Ins(17;15)insertion translocation APL and complex variant translocation APL had PML-RARα fusion gene,who responded well to ATRA and ATO treatment and had a good prognosis.