HLA class I in acute promyelocytic leukemia (APL): possible correlation with clinical outcome.
The majority of patients with acute promyelocytic leukemia (APL) possess either a bcr1 or a bcr3 type fusion between PML and RARalpha genes. The junction sequences may possibly be a target for immune response and influence susceptibility to the disease. In this case, HLA class I allele frequencies would be different between bcr1 and bcr3 patients. To test this hypothesis, we typed 102 APL patients for HLA-A, -B and -Cw alleles. The A*1, A*30, B*51, B*41, Cw*0602, and Cw*1701 alleles showed a different distribution between bcr1 and bcr3 patients, but in no case was this statistically significant after correction for the number of comparisons or was confirmed in an independent panel. Moreover, no difference was detected between bcr1 and bcr3 when HLA alleles were grouped according to their peptide binding specificities. Comparing HLA frequencies, clinical features at diagnosis and clinical outcome of the 64 patients homogeneously treated with all-trans retinoic acid and idarubicin (AIDA protocol) we observed a statistically significant association between HLA-B*13 and risk of relapse by univariate and multivariate regression analysis. Should this finding be confirmed in larger future studies, this observation would be of outmost importance in identifying patients at high risk of relapse in which more aggressive consolidation therapies should be used.
Bolognesi
E
E
Dipartimento di Scienze Mediche, Università del Piemonte Orientale A Avogadro, Novara, Italy.
Cimino
G
G
Diverio
D
D
Rapanotti
M C
MC
D'Alfonso
S
S
Fleischhauer
K
K
Migliaretti
G
G
Momigliano-Richiardi
P
P
D000328:Adult; D000951:Antigens, Neoplasm / Q000032:analysis*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015234:HLA-A Antigens / Q000032:analysis*; D015235:HLA-B Antigens / Q000032:analysis*; D059908:HLA-B13 Antigen; D015236:HLA-C Antigens / Q000032:analysis*; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D007558:Italy; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000145:classification / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000276:immunology; D014411:Neoplastic Stem Cells / Q000276:immunology; D015514:Oncogene Proteins, Fusion / Q000145:classification / Q000235:genetics*; D011379:Prognosis; D012074:Remission Induction; D012306:Risk; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage
D000951:Antigens, Neoplasm; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D059908:HLA-B13 Antigen; D015236:HLA-C Antigens; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin; D015255:Idarubicin