Opposing Mcl-1, the GALIG proapoptotic gene is upregulated as neutrophils die and underexpressed in Acute Myeloid Leukemia cells

• GALIG is a cell death-related gene nested within the human galectin-3 locus.
• GALIG pro-apoptotic function is counteracted by the anti-apoptotic Mcl-1.
• During spontaneous neutrophil apoptosis, GALIG mRNAs are up-regulated.
• In Acute Myeloid Leukemia cell samples, GALIG mRNAs are highly down-regulated.

GALIG gene expression induces apoptosis in cultured cells through a pathway still under investigation. It is highly expressed in leukocytes but weakly detectable in bone marrow, suggesting a role in the myeloid lineage homeostasis. We show here that GALIG-induced cell death is counteracted by the overexpression of MCL-1, a pro-survival member of the Bcl2 family. Moreover, during spontaneous neutrophil apoptosis, a substantial increase in GALIG gene expression is observed: GALIG still opposes MCL-1. Finally, in bone marrow and peripheral blood cells from patients with Acute Myeloid Leukemia type 2, the level of GALIG transcripts is massively down-regulated when compared to their normal counterparts, while MCL-1 is expressed to the same extent. These data suggest that GALIG could be a key player in the cell death pathway involved in leukocytes homeostasis and myeloid malignancies.

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