Contributions
Abstract: EP414
Type: E-Poster Presentation
Session title: Acute myeloid leukemia - Biology & Translational Research
Background
CALM-MLLT10 is a recurrent but rare fusion gene in leukemia and lacks relevant reports.
Aims
To investigate the cytogenetic and molecular characteristics of t(10;11)(p13;q21)/CALM-MLLT10 positive acute leukemia (AL), and to observe the clinical outcome with chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) of this molecular entity leukemia.
Methods
The G-biding karyotype and reverse transcriptase PCR results of 9627 AL cases admitted to Hebei Yanda Ludaopei Hospital from Jan. 1, 2015 to Dec. 31, 2020 were retrieved and analyzed to determine the cases positive for t(10;11)(p13;q21)/CALM-MLLT10. Eighty-six gene panel mutation screening results, RNA sequencing (RNA-seq), and clinical records of the positive cases were further analyzed.
Results
A total of 21 CALM-MLLT10 positive cases were enrolled in this cohort, including 16 males and five females, with the male-to-female ratio=3.2:1. There were 12 adults and nine children, with a median age of 24 (4-37) years. According to the lineage of leukemia, there were 12 cases of acute myeloid leukemia (AML), five T-cell acute lymphoblastic leukemia (T-ALL), one B-ALL, one mixed-phenotype AL (MPAL) with T/B antigen expressed, one MPAL with T/M antigen expressed, and one B lymphoblastic lymphoma. 91.6% (11/12) of CALM-MLLT10 positive AML cases had complex abnormal karyotypes or had additional abnormalities. PHF6 gene mutations frequently accompanied in CALM-MLLT10 positive AML cases, with an incidence of 87.5% (7/8), which is significantly higher than 3% in the CALM-MLLT10 negative AML cases, and the other frequently mutated genes include TET2, EZH2, and TP53. In CALM-MLLT10 positive T-ALL cases, JAK1/3 mutation incidence is 80%, and PHF6 mutation incidence is 40%. RNA-seq analysis showed that HOXA family genes were extensively overexpressed in CALM-MLLT10-positive AL cases. MYCN, MEIS1, SOX4, BAALC, and FLT3, which relate to poor prognosis in hematological malignancies, were also significantly overexpressed. The overall response to induction chemotherapy of these cases was poor, and 13 of them underwent allo- HSCT. Two of them underwent the second HSCT and the third HSCT, respectively, due to relapse. There were 8 cases that underwent allo-HSCT died from relapse (5 cases), infection (2 cases), and severe graft verse host disease (1 case), respectively.
Conclusion
The total incidence of CALM-MLLT10 in AL is about 0.2%, with the majority were male cases, and it can clinically manifest with AML, T-ALL, B-ALL, and MPAL. This suggests that the founder CALM-MLLT10-positive leukemia cells are at an early stage of the hematopoietic stem and progenitor cells. The accompanying PHF6, JAK1/3, and other gene mutations may synthetically determine the lineage of the leukemias. Early hematopoietic differentiation stage, complex or additional aberrant karyotypes, extensive HOXA family genes and other poor prognostic gene overexpression, high-frequency PHF6 and JAK1/3 mutations, together contributed to the poor response to chemotherapy and even poor prognosis of allo-HSCT. There is an urgent demand to find molecular targets and targeted therapy to improve this molecular entity leukemia's clinical outcome.
Keyword(s): Acute leukemia, Acute lymphoblastic leukemia, Acute myeloid leukemia, Molecular markers
Abstract: EP414
Type: E-Poster Presentation
Session title: Acute myeloid leukemia - Biology & Translational Research
Background
CALM-MLLT10 is a recurrent but rare fusion gene in leukemia and lacks relevant reports.
Aims
To investigate the cytogenetic and molecular characteristics of t(10;11)(p13;q21)/CALM-MLLT10 positive acute leukemia (AL), and to observe the clinical outcome with chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) of this molecular entity leukemia.
Methods
The G-biding karyotype and reverse transcriptase PCR results of 9627 AL cases admitted to Hebei Yanda Ludaopei Hospital from Jan. 1, 2015 to Dec. 31, 2020 were retrieved and analyzed to determine the cases positive for t(10;11)(p13;q21)/CALM-MLLT10. Eighty-six gene panel mutation screening results, RNA sequencing (RNA-seq), and clinical records of the positive cases were further analyzed.
Results
A total of 21 CALM-MLLT10 positive cases were enrolled in this cohort, including 16 males and five females, with the male-to-female ratio=3.2:1. There were 12 adults and nine children, with a median age of 24 (4-37) years. According to the lineage of leukemia, there were 12 cases of acute myeloid leukemia (AML), five T-cell acute lymphoblastic leukemia (T-ALL), one B-ALL, one mixed-phenotype AL (MPAL) with T/B antigen expressed, one MPAL with T/M antigen expressed, and one B lymphoblastic lymphoma. 91.6% (11/12) of CALM-MLLT10 positive AML cases had complex abnormal karyotypes or had additional abnormalities. PHF6 gene mutations frequently accompanied in CALM-MLLT10 positive AML cases, with an incidence of 87.5% (7/8), which is significantly higher than 3% in the CALM-MLLT10 negative AML cases, and the other frequently mutated genes include TET2, EZH2, and TP53. In CALM-MLLT10 positive T-ALL cases, JAK1/3 mutation incidence is 80%, and PHF6 mutation incidence is 40%. RNA-seq analysis showed that HOXA family genes were extensively overexpressed in CALM-MLLT10-positive AL cases. MYCN, MEIS1, SOX4, BAALC, and FLT3, which relate to poor prognosis in hematological malignancies, were also significantly overexpressed. The overall response to induction chemotherapy of these cases was poor, and 13 of them underwent allo- HSCT. Two of them underwent the second HSCT and the third HSCT, respectively, due to relapse. There were 8 cases that underwent allo-HSCT died from relapse (5 cases), infection (2 cases), and severe graft verse host disease (1 case), respectively.
Conclusion
The total incidence of CALM-MLLT10 in AL is about 0.2%, with the majority were male cases, and it can clinically manifest with AML, T-ALL, B-ALL, and MPAL. This suggests that the founder CALM-MLLT10-positive leukemia cells are at an early stage of the hematopoietic stem and progenitor cells. The accompanying PHF6, JAK1/3, and other gene mutations may synthetically determine the lineage of the leukemias. Early hematopoietic differentiation stage, complex or additional aberrant karyotypes, extensive HOXA family genes and other poor prognostic gene overexpression, high-frequency PHF6 and JAK1/3 mutations, together contributed to the poor response to chemotherapy and even poor prognosis of allo-HSCT. There is an urgent demand to find molecular targets and targeted therapy to improve this molecular entity leukemia's clinical outcome.
Keyword(s): Acute leukemia, Acute lymphoblastic leukemia, Acute myeloid leukemia, Molecular markers