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RNA sequencing of ETV6-NCOA2 expression in CD34 positive cord blood cells

ABSTRACT: Mixed-phenotype acute leukemia is a rare subtype of leukemia in which both myeloid and lymphoid markers are co-expressed on the same malignant cells. Their pathogenesis is largely unknown, and their treatment is challenging. We have previously discovered the specific association between recurrent t(8;12)(q13;p13) chromosomal translocation, creating ETV6-NCOA2 fusion, with T/Myeloid leukemias. Here we report that the ETV6-NCOA2 initiates T/Myeloid leukemia in preclinical models and examine the expression profile induced by ETV6-NCOA2 in CD34+ cord blood progenitors in-vitro.

ORGANISM(S): Homo sapiens

PROVIDER: GSE162230 | GEO | 2022/05/16

REPOSITORIES: GEO

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Project description:Objectives: Platelet derived growth factor receptor alpha (PDGFRα), which, encodes cell surface tyrosine kinase receptors for the platelet derived growth factor family undergoes different types of rearrangements creating fusion genes in myeloid neoplasms. A cryptic deletion at 4q12 creating a fusion gene FIP1L1/ PDGFRα is the most frequent change and is associated with malignant hypereosinophilia that can lead to organ damage. The other infrequent, but consistent change involving PDGFRα seen in acute myeloid leukemia (AML) and in other myeloproliferative neoplasms with eosinophilia is a t(4;12)(q12;p13) that creates a fusion gene with ETV6. This change activates ETV6 via the tyrosine kinase domain of the PDGFRα. In this report we cytogenetically characterized a new t(4;12;6) translocation which developed during transformation to AML in a patient with chronic myelomonocytic leukemia (CMML). Methods: The patient, a 70 year old male diagnosed with CMML; leukemic cells were JAK2- and ABL1/BCR/ABL1 negative and the karyotype was normal. Eight months from diagnosis the disease progressed to AML and concurrently had a low-grade follicular lymphoma. Standard G-band karyotype analysis and FISH analysis was performed to characterize the translocation to develop appropriate therapy based on genetic findings. Results: The patient was initially treated with hydroxyurea and allopurinoal, later it was changed to Azacytidine for CMML. At the time of transformation to AML, the BM karyotype showed a t(4;12;6)( q12;p13;p21.3). FISH with a tricolor 4q12 probe and ETV6 showed fusion between PDGFRα and ETV6.Concurentllty the patient had a low-grade non-Hodgkin lymphoma. Therefore the treatment was changed to imatinib for AML and high dose methylprednisolone and rituximab for lymphoma. Due to continued progression of the disease treatment was changed again to 5+2 (cytarabine 100mg/m2/day) for 5 days and idarubicin (13mg/m2/day for 2 days). Disease progressed further and the patient expired 11 months from diagnosis. Conclusion: This is the first report of development of a variant t(4;12;6) and fusion PDGFRα/ETV6 fusion that developed during transition from CMML to AML. Despite PDGFRα/ETV6 fusion the patient did not respond to imatinib.

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RNA sequencing of ETV6-NCOA2 expression in CD34 positive cord blood cells

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