The CALM/AF10 translocation is most frequently associated with T-cell acute lymphocytic leukemia (T-ALL) and also found in multiple subtypes of AML. This translocation is observed in younger patients and is associated with a poor prognosis. Our goal is to identidy a new therapeutic target(s) for CALM/AF10-driven leukemia. To determine the role of CALM (a.k.a. PICALM) in hematopoiesis and CALM/AF10-mediated leukemogenesis, we have generated a Picalm conditional knockout mouse strain. We have found that PICALM critically regulates transferrin uptake in erythroid cells by functioning as a cell-type-specific regulator of transferrin receptor (TfR) endocytosis (Ishikawa et al. Haematologica 2015).
PICALM regulates transferrin receptor endocytosis in erythroid cells.
Picalm-deficient mice demonstrate anemia as evidenced by significant reduction in red blood cell numbers, hemoglobin and hematocrit. Despite the iron-deficiency seen in red cells, serum iron levels were elevated in Picalm F/F Mx1Cre+ mice (Ishikawa et. al Haematologica 2015).
Pictures of freeze-etch EM in control and Picalm-deficient mouse splenic erythroblasts.
Formation of mature vesicles was barely observed in Picalm-deficient erythroblasts (Ishikawa et. al Haematologica 2015).