Genomics

Dataset Information

0

Identifying STRN3-RARA as a new fusion gene for acute promyelocytic leukemia [CUT&TAG]


ABSTRACT: Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia, that is generally driven by PML-RARA, resulting from a balanced chromosomal translocation t(15;17) (q24.1;q21.2). However, approximately 2% of APL patients carry other variants of RARA-fusions, which pose challenges for diagnosis and treatment. Here, we report a novel t(14;17) translocation in an APL patient that gave rise to a new fusion gene, STRN3-RARA. STRN3 forms a complex called the striatin-interacting phosphatase and kinase (STRIPAK), which couples kinases to protein phosphatase 2A and regulates their activities. Like other APL patients with RARA-variants, this patient quickly relapsed after the initial response to all-trans retinoic acid (ATRA) treatment. Mechanistically, we demonstrated that STRN3-RARA, in cooperating with UTX deficiency, which was mutated in the patient, drove APL formation in mice. Additionally, we found that STRN3-RARA cells were specifically susceptible to the TNFα pathway. Inhibition of this pathway by cepharanthine, an FDA-approved drug, effectively suppressed the growth of U937 cells with STRN3-RARA expression, as well as relapsed APL cells from the patient. Taken together, our study identified a new APL fusion gene, STRN3-RARA, and validated it as a functional APL driver, providing insight into the diagnosis and treatment of non-classic APL patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE224813 | GEO | 2024/04/23

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2024-04-23 | GSE239350 | GEO
2024-04-23 | GSE224815 | GEO
2024-04-23 | GSE224816 | GEO
2021-12-01 | GSE169521 | GEO
2012-11-08 | E-GEOD-42044 | biostudies-arrayexpress
2009-11-26 | GSE19201 | GEO
2009-12-14 | E-GEOD-19201 | biostudies-arrayexpress
2012-11-08 | E-GEOD-42118 | biostudies-arrayexpress
2012-11-08 | GSE42118 | GEO
2012-11-08 | GSE42044 | GEO