title: HS1, a Lyn kinase substrate, is abnormally expressed in B-chronic lymphocytic leukemia and correlates with response to fludarabine-based regimen.
abstract: In B-Chronic Lymphocytic Leukemia (B-CLL) kinase Lyn is overexpressed, active, abnormally distributed, and part of a cytosolic complex involving hematopoietic lineage cell-specific protein 1 (HS1). These aberrant properties of Lyn could partially explain leukemic cells' defective apoptosis, directly or through its substrates, for example, HS1 that has been associated to apoptosis in different cell types. To verify the hypothesis of HS1 involvement in Lyn-mediated leukemic cell survival, we investigated HS1 protein in 71 untreated B-CLL patients and 26 healthy controls. We found HS1 overexpressed in leukemic as compared to normal B lymphocytes (1.38±0.54 vs 0.86±0.29, p<0.01), and when HS1 levels were correlated to clinical parameters we found a higher expression of HS1 in poor-prognosis patients. Moreover, HS1 levels significantly decreased in ex vivo leukemic cells of patients responding to a fludarabine-containing regimen. We also observed that HS1 is partially localized in the nucleus of neoplastic B cells. All these data add new information on HS1 study, hypothesizing a pivotal role of HS1 in Lyn-mediated modulation of leukemic cells' survival and focusing, one more time, the attention on the BCR-Lyn axis as a putative target for new therapeutic strategies in this disorder.
authors: Venetian Institute of Molecular Medicine (VIMM), Centro di Eccellenza per la Ricerca Biomedica, Padua, Italy.
authors: Federica
authors: F
authors: Frezzato
authors: Cristina
authors: C
authors: Gattazzo
authors: Veronica
authors: V
authors: Martini
authors: Valentina
authors: V
authors: Trimarco
authors: Antonella
authors: A
authors: Teramo
authors: Samuela
authors: S
authors: Carraro
authors: Anna
authors: A
authors: Cabrelle
authors: Elisa
authors: E
authors: Ave
authors: Monica
authors: M
authors: Facco
authors: Renato
authors: R
authors: Zambello
authors: Elena
authors: E
authors: Tibaldi
authors: Anna Maria
authors: AM
authors: Brunati
authors: Gianpietro
authors: G
authors: Semenzato
authors: Livio
authors: L
authors: Trentin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology; D003520:Cyclophosphamide / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology; D013379:Substrate Specificity / Q000187:drug effects; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001798:Blood Proteins; C061909:HCLS1 protein, human; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D003520:Cyclophosphamide; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D014740:Vidarabine; C024352:fludarabine