Abstract
BackgroundAcute myeloid leukemia (AML) is a heterogeneous clonal disorder in terms of cytogenetic and molecular aberrations. Ten-Eleven-Translocation 2 (TET2), Kirsten rat sarcoma viral oncogene homolog (KRAS), and Casitas B-cell lymphoma (CBL) have an important role pathogenesis of acute myeloid leukemia (AML) and their activated mutations confer proliferative and survival signals. AimIn this study, we aimed to find possible genetic markers for molecular analysis in childhood AML by screening hot-spot exons of TET2, KRAS, and CBL using Next Generation Sequencing (NGS) analysis. In addition, association between found variants and mutations of Januse Kinase-2 (JAK2) and Fms-Related Tyrosine Kinase (FLT3) were analyzed which are important prognostic risk factors for AML. MethodsEight patients who were diagnosed with pediatric AML at Losante Pediatric Hematology–Oncology Hospital were included to the study. Hot-spot exons of TET2, KRAS and CBL genes were screened using the NGS method. Furthermore, FLT3-Internal Tandem Duplicate (FLT3-ITD) and JAK2-V617F were analyzed by Real Time Polymerase chain Reaction (Real Time-PCR). ResultsIn total, we identified 20 variants in studied genes by NGS. In our patient group, 16 variants in the TET2 (seven novel, seven missense and two silent), two variants in the KRAS (one missense and one intronic) and two variants in the CBL (two novel) were found. All of AML patients were found negative for JAK V617 F. Three of the eight patients (37.5%) showed mutations of both FLT3-ITD and TET2, KRAS, CBL. ConclusionWe found novel mutations for TET2, KRAS, and CBL. The detected variants in this article seem to be the first screening results of genes studied by NGS in childhood AML patients. Our results also showed some degree of association between FLT3-ITD and TET2, KRAS, CBL mutations.
Highlights
Acute myeloid leukemia (AML) is a heterogeneous clonal neoplasm characterized by accumulated genetic aberrations, which causes enhanced proliferation, maturation arrest, increased survival of the leukemic blast cells and variable response to therapy [1,2,3,4,5].During the past decades, a number of recurrent cytogenetic and molecular genetic abnormalities have been identified in AML such as t(8;21), inv(16), FMS-like tyrosine kinase 3 (FLT3), NPM1, CEBPA, Ten-Eleven-Translocation 2 (TET2), Kirsten rat sarcoma viral oncogene homolog (KRAS), and CBL.TET family gene members (TET1, TET2, and TET3) have functions mostly in hematopoietic differentiation
The detected variants in this article seem to be the first screening results of genes studied by Next Generation Sequencing (NGS) in childhood AML patients
Our results showed some degree of association between FLT3-ITD and TET2, KRAS, CBL mutations
Summary
AML is a heterogeneous clonal neoplasm characterized by accumulated genetic aberrations, which causes enhanced proliferation, maturation arrest, increased survival of the leukemic blast cells and variable response to therapy [1,2,3,4,5].During the past decades, a number of recurrent cytogenetic and molecular genetic abnormalities have been identified in AML such as t(8;21), inv(16), FLT3, NPM1, CEBPA, TET2, KRAS, and CBL.TET family gene members (TET1, TET2, and TET3) have functions mostly in hematopoietic differentiation. AML is a heterogeneous clonal neoplasm characterized by accumulated genetic aberrations, which causes enhanced proliferation, maturation arrest, increased survival of the leukemic blast cells and variable response to therapy [1,2,3,4,5]. A number of recurrent cytogenetic and molecular genetic abnormalities have been identified in AML such as t(8;21), inv(16), FLT3, NPM1, CEBPA, TET2, KRAS, and CBL. Acute myeloid leukemia (AML) is a heterogeneous clonal disorder in terms of cytogenetic and molecular aberrations. Ten-Eleven-Translocation 2 (TET2), Kirsten rat sarcoma viral oncogene homolog (KRAS), and Casitas B-cell lymphoma (CBL) have an important role pathogenesis of acute myeloid leukemia (AML) and their activated mutations confer proliferative and survival signals
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