HLA class I in acute promyelocytic leukemia (APL): possible correlation with clinical outcome

Abstract

The majority of patients with acute promyelocytic leukemia (APL) possess either a bcr1 or a bcr3 type fusion between PML and RAR␣ 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. Leukemia (2000) 14, 393-398.

Is there any genetic susceptibility to acute promyelocytic leukemia?

“…Previous studies concluded that there was no evidence of an HLA-linked leukemia susceptibility gene in AML, while other reports found a significant association with Cw4 or a decrease in A19, or claimed an increase in intra-HLA recombination in the families of leukemia patients. 3 Bolognesi et al's series, 1 as well as ours, did not show significant differences in HLA phenotypes among APL patients and an ethnically matched control population. However, the percentage of our patients expressing HLA-Cw4 was higher than expected (Table 3).…”

CD34 expression is associated with poor clinical outcome in patients with acute promyelocytic leukemia

“…Male sex has an unfavorable outcome compared with female sex [18]. In a recent study, HLA-B13 was associated with a high risk of relapse [19]. Immunophenotypic markers, such as CD34 and CD56, are considered prognostic factors, but there is still controversy over their clinical implications [12].…”

Adaptive immunity cooperates with liposomalall-trans-retinoic acid (ATRA) to facilitate long-term molecular remissions in mice with acute promyelocytic leukemia

“…Murine APL cells do not seem to be immunologically ''cloaked,'' nor are they resistant to clearance in vivo. Similarly, limited studies of human APL cells have revealed that nearly all express Class I, and that a significant proportion express Class II (26)(27)(28). It is not yet known whether human APL cells can elicit effective immune responses in vivo, but it is reasonably clear that APL patients do not contain cytotoxic T lymphocytes (CTL) that recognize unique high affinity peptides from the PML-RAR␣ junction region (29)(30)(31).…”