Loss of SMAD1 in acute myeloid leukemia with <i>KMT2A::AFF1</i> and <i>KMT2A::MLLT3</i> fusion genes.

ABSTRACT:

Introduction

KMT2A-rearrangements define a subclass of acute leukemias characterized by a distinct gene expression signature linked to the dysfunctional oncogenic fusion proteins arising from various chromosomal translocations involving the KMT2A (also known as MLL1) gene. Research on the disease pathomechanism in KMT2A-rearranged acute leukemias has mainly focused on the upregulation of the stemness-related genes of the HOX-family and their co-factor MEIS1.

Results

Here we report the KMT2A::AFF1 and KMT2A::MLLT3 fusion gene-dependent downregulation of SMAD1, a TGF-β signaling axis transcription factor. SMAD1 expression is lost in the majority of AML patient samples and cell lines containing the two fusion

SUBMITTER: Dietsche L 

PROVIDER: S-EPMC11743462 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature