title: Cellular proteolytic modification of tumor-suppressor CYLD is critical for the initiation of human T-cell acute lymphoblastic leukemia.
abstract: There exists a general recognition of the fact that post translational modification of CYLD protein through proteolytic cleavage by MALT-1 results in sustained cellular NF-kB activity which is conspicuously found to be associated with cancer in general and hematological malignancies in particular. The present study was directed to understand the contribution of MALT-1 and deubiquitinase CYLD to the initiation of T-cell acute lymphoblastic leukemia (T-ALL). Such a study revealed for the first time that the 35kDa CYLD cleaved factor generated by MALT-1 mediated proteolytic cleavage was conspicuously present in human T- ALL subjects of pediatric age group. Further, over-expression of this 35kDa CYLD factor within normal human peripheral blood mononuclear cells had the inherent capacity to program the genome of these cells resulting in T-cell lineage ALL. Based upon these results, we propose that MALT1 inhibitors may be of crucial importance in the treatment of T-ALL subjects of pediatric age group.
authors.affiliation: Department of Experimental Medicine & Biotechnology, Post-Graduate Institute of Medical Education & Research, Chandigarh 160012, India.
authors.forename: Mansi
authors.initials: M
authors.lastname: Arora
authors.affiliation: Department of Experimental Medicine & Biotechnology, Post-Graduate Institute of Medical Education & Research, Chandigarh 160012, India. Electronic address: dkaul_24@hotmail.com.
authors.forename: Deepak
authors.initials: D
authors.lastname: Kaul
authors.affiliation: Department of Hematology, Post-graduate Institute of Medical Education & Research, Chandigarh 160012, India.
authors.forename: Neelam
authors.initials: N
authors.lastname: Varma
authors.affiliation: Department of Pediatrics, Post-graduate Institute of Medical Education & Research, Chandigarh 160012, India.
authors.forename: R K
authors.initials: RK
authors.lastname: Marwaha
mesh_terms: D000293:Adolescent; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D000074749:Deubiquitinating Enzyme CYLD; D005260:Female; D006801:Humans; D008297:Male; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism*; D046188:Protein Modification, Translational; D059748:Proteolysis; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
keywords: CYLD cleavage; Human PBMCs; MALT1; Pediatric T-ALL; Transformation