Relevance of CD49d protein expression as overall survival and progressive disease prognosticator in chronic lymphocytic leukemia.
CD49d/alpha4-integrin is variably expressed in chronic lymphocytic leukemia (CLL). We evaluated its relevance as independent prognosticator for overall survival and time to treatment (TTT) in a series of 303 (232 for TTT) CLLs, in comparison with other biologic or clinical prognosticators (CD38, ZAP-70, immunoglobulin variable heavy chain (IGHV) gene status, cytogenetic abnormalities, soluble CD23, beta2-microglobulin, Rai staging). Flow cytometric detection of CD49d was stable and reproducible, and the chosen cut-off (30% CLL cells) easily discriminated CD49dlow from CD49dhigh cases. CD49d, whose expression was strongly associated with that of CD38 (P<.001) and ZAP-70 (P<.001), or with IGHV mutations (P<.001), was independent prognosticator for overall survival along with IGHV mutational status (CD49d hazard ratio, HRCD49d=3.52, P=.02; HRIGHV=6.53, P<.001) or, if this parameter was omitted, with ZAP-70 (HRCD49d=3.72, P=.002; HRZAP-70=3.32, P=.009). CD49d was also a prognosticator for TTT (HR=1.74, P=.007) and refined the impact of all the other factors. Notably, a CD49dhigh phenotype, although not changing the outcome of good prognosis (ZAP-70low, mutated IGHV) CLL, was necessary to correctly prognosticate the shorter TTT of ZAP-70high (HR=3.12; P=.023) or unmutated IGHV (HR=2.95; P=.002) cases. These findings support the introduction of CD49d detection in routine prognostic assessment of CLL patients, and suggest both pathogenetic and therapeutic implications for CD49d expression in CLL.
Gattei
Valter
V
Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, Istituto di Ricovero e Cura a Carattere Scientifico Aviano, Italy. vgattei@cro.it
Bulian
Pietro
P
Del Principe
Maria Ilaria
MI
Zucchetto
Antonella
A
Maurillo
Luca
L
Buccisano
Francesco
F
Bomben
Riccardo
R
Dal-Bo
Michele
M
Luciano
Fabrizio
F
Rossi
Francesca M
FM
Degan
Massimo
M
Amadori
Sergio
S
Del Poeta
Giovanni
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics; D006801:Humans; D039441:Integrin alpha4 / Q000096:biosynthesis* / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D010641:Phenotype; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D015996:Survival Rate
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D039441:Integrin alpha4