Contributions
Abstract: EP339
Type: E-Poster Presentation
Session title: Acute lymphoblastic leukemia - Biology & Translational Research
Background
TAF15-ZNF384 is a recurrent but rare fusion gene in leukemia and lacks relevant reports.
Aims
To investigate the laboratory characteristics and clinical outcomes of acute leukemia (AL) with t(12;17)(p13;q21)/TAF15-ZNF384.
Methods
Laboratory examination results and clinical records of t(12;17)(p13;q21)/TAF15-ZNF384 positive cases admitted to Hebei Yanda Ludaopei Hospital from Feb.1, 2009 to Nov. 30, 2020 were retrieved and analyzed, including G-banding karyotyping, flow cytometry, fluorescence in situ hybridization (FISH, ZNF384 separation probe), RNA sequencing (RNA-seq), PCR, gene panel mutation screening, as well as routine inspections.
Results
A total of 12 positive cases were enrolled in this cohort, including 8 males and 4 females, with a median age of 25.5 (3-49) years. Eight cases had complete blood count records at the time of disease onset, and the white blood cell count ranged 1.58-38×109/L. Immunophenotyping showed that 11 cases were acute B lymphocytic leukemia (B-ALL) with myeloid antigen expression, and 1 was mixed-phenotype AL with B/myeloid lineage markers. All cases expressed CD19, CD34, CD13 and/or CD33, 10 cases expressed CD22, 7 cases expressed or partially expressed CD10, and only 1 case weakly expressed CD20. Nine cases were positive for t(12;17)(p13;q21) at the disease onset or relapse, and 7 of them with additional chromosomal abnormalities (CAs). Among the 3 cases with t(12;17)(p13;q21) negative, 1 was normal karyotype, 1 was complex karyotype (CK) with t(11;17)(q21;q21) and ectopic 12p12, and 1 was t(5;17) )(p12;p11.2) with additional CAs. All of them were tested positive for TAF15-ZNF384 transcript by RNA-seq and PCR. FISH detection showed 9 cases with typical ZNF384 separation signals, 1 case lost 1 ZNF384 signal, 1 CK case lost partial of one ZNF384 signal, and 1 normal karyotype case also showed a normal FISH signal. RNA-seq and PCR analysis identified TAF15 exon6-ZNF384 exon3 transcript in these 3 cases who manifested atypical FISH signal. TAF15-ZNF384 transcripts were analyzed by RNA-seq and PCR in 7 cases, there were 4 TAF15 exon6-ZNF384 exon3, 2 TAF15 exon9-ZNF384 exon3, and 1 TAF15 exon11-ZNF384 exon3 (Fig.1 A). Ten cases underwent 86 gene panel mutation analyses, 8 of them carried FLT3-PTPN11-CBL-NRAS/KRAS-NF1 pathway mutations, and other mutation genes included ETV6, TET2, and KMT2D. Induction and consolidation chemotherapy mainly include VDCLP/CVDP/CAM/VDLP/asparaginase and methotrexate (Fig.1 B). The overall response to induction chemotherapy was favorable, except for one case, which failed to achieve complete remission (CR). However, 9 cases relapsed during consolidation chemotherapy, and 5 of them relapsed within 8 months after diagnosis. Four cases underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Two cases who underwent salvage HSCT relapsed 3 months and 6 months after transplantation, respectively; the other 2 cases had been followed up after HSCT and survived without relapse for 63 months and 13 months, respectively.
Conclusion
AL cases with (12;17)(p13;q21)/TAF15-ZNF384 have unique genetic and immunophenotypic characteristics. They are often accompanied by FLT3-PTPN11-CBL-NRAS/KRAS-NF1 pathway mutations. There is a significant t(12;17)(p13;q21) negative rate, which may be attributed to CK and cryptic ectopic; RNA-seq and PCR analysis can help to ensure the detection rate. The immunophenotype is mostly B-ALL with myeloid antigen expression. The general response to conventional chemotherapy is favorable, but prone to relapse. Cases of this sub-entity may benefit from allo-HSCT at the first CR.
Keyword(s): Acute lymphoblastic leukemia, Allogeneic hematopoietic stem cell transplant, Translocation
Abstract: EP339
Type: E-Poster Presentation
Session title: Acute lymphoblastic leukemia - Biology & Translational Research
Background
TAF15-ZNF384 is a recurrent but rare fusion gene in leukemia and lacks relevant reports.
Aims
To investigate the laboratory characteristics and clinical outcomes of acute leukemia (AL) with t(12;17)(p13;q21)/TAF15-ZNF384.
Methods
Laboratory examination results and clinical records of t(12;17)(p13;q21)/TAF15-ZNF384 positive cases admitted to Hebei Yanda Ludaopei Hospital from Feb.1, 2009 to Nov. 30, 2020 were retrieved and analyzed, including G-banding karyotyping, flow cytometry, fluorescence in situ hybridization (FISH, ZNF384 separation probe), RNA sequencing (RNA-seq), PCR, gene panel mutation screening, as well as routine inspections.
Results
A total of 12 positive cases were enrolled in this cohort, including 8 males and 4 females, with a median age of 25.5 (3-49) years. Eight cases had complete blood count records at the time of disease onset, and the white blood cell count ranged 1.58-38×109/L. Immunophenotyping showed that 11 cases were acute B lymphocytic leukemia (B-ALL) with myeloid antigen expression, and 1 was mixed-phenotype AL with B/myeloid lineage markers. All cases expressed CD19, CD34, CD13 and/or CD33, 10 cases expressed CD22, 7 cases expressed or partially expressed CD10, and only 1 case weakly expressed CD20. Nine cases were positive for t(12;17)(p13;q21) at the disease onset or relapse, and 7 of them with additional chromosomal abnormalities (CAs). Among the 3 cases with t(12;17)(p13;q21) negative, 1 was normal karyotype, 1 was complex karyotype (CK) with t(11;17)(q21;q21) and ectopic 12p12, and 1 was t(5;17) )(p12;p11.2) with additional CAs. All of them were tested positive for TAF15-ZNF384 transcript by RNA-seq and PCR. FISH detection showed 9 cases with typical ZNF384 separation signals, 1 case lost 1 ZNF384 signal, 1 CK case lost partial of one ZNF384 signal, and 1 normal karyotype case also showed a normal FISH signal. RNA-seq and PCR analysis identified TAF15 exon6-ZNF384 exon3 transcript in these 3 cases who manifested atypical FISH signal. TAF15-ZNF384 transcripts were analyzed by RNA-seq and PCR in 7 cases, there were 4 TAF15 exon6-ZNF384 exon3, 2 TAF15 exon9-ZNF384 exon3, and 1 TAF15 exon11-ZNF384 exon3 (Fig.1 A). Ten cases underwent 86 gene panel mutation analyses, 8 of them carried FLT3-PTPN11-CBL-NRAS/KRAS-NF1 pathway mutations, and other mutation genes included ETV6, TET2, and KMT2D. Induction and consolidation chemotherapy mainly include VDCLP/CVDP/CAM/VDLP/asparaginase and methotrexate (Fig.1 B). The overall response to induction chemotherapy was favorable, except for one case, which failed to achieve complete remission (CR). However, 9 cases relapsed during consolidation chemotherapy, and 5 of them relapsed within 8 months after diagnosis. Four cases underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Two cases who underwent salvage HSCT relapsed 3 months and 6 months after transplantation, respectively; the other 2 cases had been followed up after HSCT and survived without relapse for 63 months and 13 months, respectively.
Conclusion
AL cases with (12;17)(p13;q21)/TAF15-ZNF384 have unique genetic and immunophenotypic characteristics. They are often accompanied by FLT3-PTPN11-CBL-NRAS/KRAS-NF1 pathway mutations. There is a significant t(12;17)(p13;q21) negative rate, which may be attributed to CK and cryptic ectopic; RNA-seq and PCR analysis can help to ensure the detection rate. The immunophenotype is mostly B-ALL with myeloid antigen expression. The general response to conventional chemotherapy is favorable, but prone to relapse. Cases of this sub-entity may benefit from allo-HSCT at the first CR.
Keyword(s): Acute lymphoblastic leukemia, Allogeneic hematopoietic stem cell transplant, Translocation