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Is the c‐Cbl Proto‐Oncogene Involved in Chronic Lymphocytic Leukemia?
Author(s) -
MANKAÏ AMANI,
EVEILLARD JEANRICHARD,
BUHÉ VIRGINIE,
LE STER KARINE,
LOISEL SÉVERINE,
GHEDIRA IBTISSEM,
YOUINOU PIERRE,
BERTHOU CHRISTIAN,
BORDRON ANNE
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1381.021
Subject(s) - chronic lymphocytic leukemia , cancer research , breakpoint cluster region , oncogene , cd5 , leukemia , biology , signal transduction , lymphoma , chemistry , immunology , cancer , microbiology and biotechnology , receptor , cell cycle , genetics
: Chronic lymphocytic leukemia (CLL) is characterized by survival advantage and accumulation of CD5+ mature B lymphocytes. Expression of zeta‐chain‐associated protein‐70 (ZAP‐70), normally present in T lymphocytes or immature B cells, is associated with disease aggressiveness, as IgVH mutational status, and some proteins implicated in survival signal pathways are found to be constitutively activated in CLL cells. ZAP‐70 signaling is regulated through molecular adaptors, such as the proto‐oncogene product c‐Casitas B lineage lymphoma (c‐Cbl). The aim of this study was to determine the implication of this proto‐oncogene product in CLL in survival signals. It appeared that expression of c‐Cbl was increased in CLL and not correlated to that of B cell linker protein or ZAP‐70. Furthermore, c‐Cbl was significantly hypophosphorylated in progressive disease, so that hypophosphorylated form of c‐Cbl (c‐Cbl.P) along with ZAP‐70, set a cutoff ratio distributing patients with stable situation below 1, and those with progressive disease equal or above 1. Given that phospholipase gamma 2 (PLCγ2) function is also influenced by c‐Cbl hypophosphorylation, the ratio of PLCγ2 to c‐Cbl.P was measured in CLL B cells and consistently found to be ≥ 1 in Binet stage B CLL patients, as opposed to stage A CLL patients. These findings invite analysis of the role of c‐Cbl in CLL.