Increased μ-Calpain Activity in Blasts of Common B-Precursor Childhood Acute Lymphoblastic Leukemia Correlates with Their Lower Susceptibility to Apoptosis

PloS One
Anna MikosikJacek M Witkowski

Abstract

Childhood acute lymphoblastic leukemia (ALL) blasts are characterized by inhibited apoptosis promoting fast disease progress. It is known that in chronic lymphocytic and acute myeloid leukemias the reduced apoptosis is strongly related with the activity of calpain-calpastatin system (CCS) composed of cytoplasmic proteases--calpains--performing the modulatory proteolysis of key proteins involved in cell proliferation and apoptosis, and of their endogenous inhibitor--calpastatin. Here, the CCS protein abundance and activity was for the first time studied in childhood ALL blasts and in control bone marrow CD19+ B cells by semi-quantitative flow cytometry and western blotting of calpastatin fragments resulting from endogenous calpain activity. Significantly higher μ-calpain (CAPN1) gene transcription, protein amounts and activity (but not those of m-calpain), with calpastatin amount and transcription of its gene (CAST) greatly varying were observed in CD19(+) ALL blasts compared to control cells. Significant inverse relation between the amount/activity of calpain and spontaneous apoptosis was noted. Patients older than 10 years (considered at higher risk) displayed increased amounts and activities of blast calpain. Finally, treatme...Continue Reading

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Citations

Nov 12, 2016·Oncotarget·Anna MikosikJacek M Witkowski
Jan 24, 2021·Immunologic Research·Yueqi ChenFang Liu
Jan 10, 2021·Mechanisms of Ageing and Development·Jacek M WitkowskiTamas Fulop

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Methods Mentioned

BETA
bone marrow aspiration
biopsy
biopsies
density gradient centrifugation
FACS
PCR

Software Mentioned

STATISTICA
Cyflogic
CellQuest
Scion Image Beta
Labworks Image Acquisition and Analysis
LightCycler

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