MilliporeSigma
  • Home
  • Search Results
  • A Drosophila model identifies calpains as modulators of the human leukemogenic fusion protein AML1-ETO.

A Drosophila model identifies calpains as modulators of the human leukemogenic fusion protein AML1-ETO.

Proceedings of the National Academy of Sciences of the United States of America (2009-07-08)
Dani Osman, Vanessa Gobert, Frida Ponthan, Olaf Heidenreich, Marc Haenlin, Lucas Waltzer
ABSTRACT

The t(8:21)(q22;q22) translocation is 1 of the most common chromosomal abnormalities linked to acute myeloid leukemia (AML). AML1-ETO, the product of this translocation, fuses the N-terminal portion of the RUNX transcription factor AML1 (also known as RUNX1), including its DNA-binding domain, to the almost entire transcriptional corepressor ETO (also known as MTG8 or RUNX1T1). This fusion protein acts primarily by interfering with endogenous AML1 function during myeloid differentiation, although relatively few genes are known that participate with AML1-ETO during leukemia progression. Here, we assessed the consequences of expressing this chimera in Drosophila blood cells. Reminiscent of what is observed in AML, AML1-ETO specifically inhibited the differentiation of the blood cell lineage whose development depends on the RUNX factor Lozenge (LZ) and induced increased numbers of LZ(+) progenitors. Using an in vivo RNAi-based screen for suppressors of AML1-ETO, we identified calpainB as required for AML1-ETO-induced blood cell disorders in Drosophila. Remarkably, calpain inhibition triggered AML1-ETO degradation and impaired the clonogenic potential of the human t(8;21) leukemic blood cell line Kasumi-1. Therefore Drosophila provides a promising genetically tractable model to investigate the conserved basis of leukemogenesis and to open avenues in AML therapy.

MATERIALS
Product Number
Brand
Product Description

SAFC
RPMI-1640 Medium, Hybri-Max, Modified, with L-glutamine, 4500 mg/L glucose and 15mM HEPES, without sodium bicarbonate, powder, suitable for hybridoma
Sigma-Aldrich
RPMI-1640 Medium, Modified, with sodium bicarbonate, without methionine, cystine and L-glutamine, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
RPMI-1640 Medium, Dutch Modification, with sodium bicarbonate and 20mM HEPES, without L-glutamine, liquid, sterile-filtered, suitable for cell culture
SAFC
RPMI-1640 Medium, 10 ×, Without L-glutamine, folic acid and sodium bicarbonate, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
RPMI-1640 Medium, Modified, with 20 mM HEPES and L-glutamine, without sodium bicarbonate, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
RPMI-1640 Medium, With L-glutamine, without glucose and sodium bicarbonate, powder, suitable for cell culture
SAFC
RPMI-1640 Medium, AutoMod, without L-glutamine and sodium bicarbonate, powder, suitable for cell culture
Sigma-Aldrich
RPMI-1640 Medium, With L-glutamine and sodium bicarbonate, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Thiazolyl Blue Tetrazolium Bromide, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥97.5% (HPLC)
Sigma-Aldrich
Thiazolyl Blue Tetrazolium Bromide, 98%
Sigma-Aldrich
RPMI-1640 Medium, With sodium bicarbonate, without L-glutamine, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
RPMI-1640 Medium, Modified, with sodium bicarbonate, without L-glutamine and phenol red, liquid, sterile-filtered, suitable for cell culture
SAFC
RPMI-1640 Medium, HEPES Modification, with L-glutamine and 25mM HEPES, without sodium bicarbonate, powder, suitable for cell culture
SAFC
RPMI-1640 Medium, HEPES Modification, With 25 mM HEPES, without L-glutamine., liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
RPMI-1640 Medium, With L-glutamine, without sodium bicarbonate, powder, suitable for cell culture
Sigma-Aldrich
RPMI-1640 Medium, Modified, with L-glutamine, without phenol red and sodium bicarbonate, powder, suitable for cell culture
Sigma-Aldrich
RPMI-1640 Medium, With L-glutamine and sodium bicarbonate. Without arginine, leucine, lysine, and phenol red, liquid, sterile-filtered, suitable for cell culture, designed for isotope labeling for cell culture applications
Sigma-Aldrich
StableCell RPMI-1640, With stable glutamine and sodium bicarbonate, liquid, sterile-filtered, suitable for cell culture
SAFC
RPMI-1640 Medium, with 2.05 mM L-glutamine, with 25mM HEPES, liquid, sterile-filtered, suitable for cell culture