Abstract

HLX in AML: novel prognostic and therapeutic target.

Highlights

  • Acute myeloid leukemia (AML) is an aggressive hematological malignancy with poor clinical outcome in most subtypes of the disease

  • We found that pre-leukemic hematopoietic stem and progenitor cells (HSPC) have 4-fold elevation of Hlx expression, suggesting that Hlx overexpression is an early event in leukemogenesis and Hlx is involved in malignant transformation [1]

  • Overexpression of HLX in HSPC in vitro led to a myeloid differentiation block and to formation of phenotypically similar, aberrant myeloid progenitors with unlimited serial clonogenicity. These results indicate that HLX suppresses the function of normal immature hematopoietic stem cells (HSC) and progenitors but leads to a differentiation block and confers unlimited clonogenic capacity at the level of phenotypically more mature progenitors

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Summary

Introduction

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with poor clinical outcome in most subtypes of the disease. In order to identify genes involved early on in leukemogenesis, we analyzed gene expression changes in sorted hematopoietic stem and progenitor cells (HSPC) isolated during the pre-leukemic stage from bone marrow of animals of the PU.1 URE(upstream regulatory element)∆/∆ model of AML [6]. We found that pre-leukemic HSPC have 4-fold elevation of Hlx expression, suggesting that Hlx overexpression is an early event in leukemogenesis and Hlx is involved in malignant transformation [1].

Results
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