HLA-DR antigen-negative acute myeloid leukemia

Abstract

Human leukocyte antigen (HLA) Class II antigens are variably expressed on acute myeloid leukemia (AML) blasts. The biological and clinical significance of HLA Class II antigen expression by AML cells is not known. Therefore, we sought to characterize cases of AML without detectable HLA-DR expression. Samples from 248 consecutive adult AML patients were immunophenotyped by multiparameter flow cytometry at diagnosis. HLA-DR antigens were not detected on AML cells from 43 patients, including 20 with acute promyelocytic leukemia (APL), and 23 with other subtypes of AML. All APL cases had t(15;17), but there were no characteristic chromosome abnormalities in non-APL cases. No direct expression of other antigens was identified in HLA-DR-negative APL and non-APL cases. Interestingly, cells from three HLA-DR-negative non-APL patients had similar morphology to that of the hypogranular variant of APL. This morphology, however, was not present in any HLA-DR-positive AML cases. Treatment response was similar in the 23 HLA-DR-negative non-APL and the 205 HLA-DR-positive patients. Finally, relapse was infrequently associated with changes in HLA-DR antigen expression, as the HLA-DR antigen was lost at relapse in only 4% of HLA-DR-positive cases, and was gained at relapse in only 17% of HLA-DR-negative cases. We conclude that HLA-DR-negative AML includes approximately equal numbers of APL and non-APL cases, and that the morphology of HLA-DR-negative non-APL cases can mimic the hypogranular variant of APL. The diagnosis of APL cannot be based on morphology and lack of HLA-DR antigen expression; rather, it requires cytogenetic or molecular confirmation.

Inactivation of class II transactivator by DNA methylation and histone deacetylation associated with absence of HLA-DR induction by interferon-γ in haematopoietic tumour cells

“…It is now known that some haematopoietic tumour cells do not express the MHC class II antigen HLA-DR (Kraiba et al, 1989;Wetzler et al, 2003), though the reason why remains unclear. In the present study, we examined expression HLA-DR and coactivators of MHC class II molecules, as well as the effects DNA methylation and histone deacetylation, in a group of human haematopoietic tumour cell lines.…”

A distinctive nuclear morphology in acute myeloid leukemia is strongly associated with loss of HLA-DR expression and FLT3 internal tandem duplication

“…That abstract described 74 cases of AML of the French-AmericanBritish (FAB) M1 subtype, in which 17 cases (23%) demonstrated cup-like nuclear invagination, myeloperoxidase staining, loss of HLA-DR and CD34, frequent aberrant CD56, and a normal karyotype, similar to our CD34-negative cases. The two published papers that appear to describe a small number of similar cases include a relatively recent description of HLA-DRnegative AMLs, 22 which noted that three of 23 t(15;17)-negative, HLA-DR-negative cases showed nuclear folding or convolution, occurred among female subjects, and had normal karyotypes, reminiscent of AML-cuplike. Unfortunately, that study did not describe the morphology of these three cases in adequate detail to determine whether cup-like nuclear invagination was a feature.…”

HLA‐DRneg patients without acute promyelocytic leukemia show distinct immunophenotypic, genetic, molecular, and cytomorphologic characteristics compared to acute promyelocytic leukemia

“…These HLA-DR neg non-APL cases (further referred to as DR À AML in contrast to APL and DR þ AML) often resemble cytomorphologic features of hypogranular APL and belong almost exclusively to the myeloid AML subtypes (7,9,16). Published studies comparing APL and DR À AML cases with respect to CD34 expression and lineage infidelity, i.e., detecting the expression of CD2, CD56, CD19, or CD7, reported discrepant results (7,9,(15)(16)(17).…”

“…Besides the 8 to 17% of APL among all patients with AML, an additional 1.2 to 21% of HLA-DR neg AML without the PML-RARa fusion gene have been described (7,9,(15)(16)(17). These HLA-DR neg non-APL cases (further referred to as DR À AML in contrast to APL and DR þ AML) often resemble cytomorphologic features of hypogranular APL and belong almost exclusively to the myeloid AML subtypes (7,9,16).…”