PB1716 CLINICAL AND GENETIC FEATURES AND PROGNOSIS ANALYSIS OF PATIENTS WITH RECURRENT GENETIC ABNORMALITY T(12;22) (P13;Q12)
Authors: T. Wang, X. Ma, S. Hui, J. Ni, Y. Yin, W. Cao, Y. Zhang, X. Wang, X. Chen, H. Liu
Journal: HemaSphere (2019)

Background: Cytogenetic abnormality is an important basis for prognostic stratification of acute leukemia. Chromosome translocation t(12;22)(p13;q12) and MN1‐ETV6/ETV6‐MN1 fusion was reported to be a recurrent genetic abnormality in acute myeloid leukemia (AML) / myelodysplastic syndrome (MDS) but only found in 12 cases to date. The clinical and genetic characteristics of t(12;22)(p13;q12) are not fully understood and therapeutic effect of allogeneic hematopoietic stem cell transplantation (allo‐HSCT) has not been reported. Aims: To investigate the clinical and laboratory features and prognosis of 9 newly diagnosed patients with hematological malignancies carrying recurrent genetic abnormality t(12;22)(p13;q12) who were treated with chemotherapy and allo‐HSCT. Methods: Genetic abnormalities were analyzed by conventional G‐banding karyotype analysis, fluorescence in situ hybridization testing (FISH), reverse transcription polymerase chain reaction (RT‐PCR), and targeted next‐generation sequencing. Patients were treated with IA (idarubicin plus cytarabine)/MHA (mitoxantrone homoharring tonine cytarabine)/HA(homo harringtonine cytarabine) combined with DAC (decitabine) and allo‐HSCT. Results: A total of 8 patients with t(12;22)(p13;q12) and one patient with t(12;17;22)(p13;q21;q12) were found in routine karyotype analysis out of 2782 AML/MDS patients in our hospital from April 2012 to October 2018, including 1 AML‐M2, 1 AML‐M4, 2 AML‐M5, 2 mixed phenotype acute leukemia (MPAL), 1 AML transformed from MDS, 1 MDS‐RAEB2, and 1 chronic myelomonocytic leukemia (CMML). All patients were younger than 60 years old with a median age of 45 years and 2 of them were children (aged 4 and 11 years old). Additional abnormalities were found in 5 of the 8 cases with t(12;22)(p13;q12), all of the 5 cases with trisome 8 and 4 have complex chromosome abnormalities. MN1‐ETV6 and/or ETV6‐MN1 fusion transcript was confirmed by RT‐PCR in 7 of the 9 patients. Additional FISH experiments were performed using MN1 and ETV6 dual color break apart rearrangement probes in the remaining 2 cases. Split signals were detected in both probes, indicating breakpoints in MN1 and ETV6 genes and atypical fusions between the two genes. Mutation analysis of 86 genes frequently mutated in hematologic malignancies showed that SRSF2 and STAT2 mutations were identified in 1 case with MDS; FLT3, KIT, NPM1, DNMT3A, TET2, and RUNX1 mutations were detected in 1 patient with AML; no specific gene mutation was found in other cases. After the first course of treatment, only one patient achieved hematological complete remission (CR). allo‐HSCT was performed in six patients. One of them lost follow‐up after 7 months. The other 5 patients have survived for 37 months, 47 months, 45 months, 27 months and 16 months from diagnosis, respectively, at the end of follow‐up. 3 cases did not undergo transplantation. One of them lost follow‐up, the other 2 have survived for 3 months and 11 months, respectively, at the end of follow‐up. Summary/Conclusion: Nearly 1/3 of patients with t(12;22)(p13;q12) abnormality show simple translocation, +8 was the highly concomitant additional cytogenetic abnormalities. Given the poor response to conventional and strong chemotherapy, allo‐HSCT should be performed to improve the curative effect and prolong the overall survival of the patients since its curative effect is far superior to chemotherapy.