High Ia (HLA-DR) and low CD11b (Mo1) expression may predict early conversion to leukemia in myelodysplastic syndromes

Abstract

The FAB classification of myelodysplastic syndromes (MDS) has been useful in predicting prognosis; however, additional methods are required to detect patients at high risk for early conversion to acute nonlymphoblastic leukemia (ANLL). Using a panel of monoclonal antibodies to myelomonocytic surface antigens (MMSA) and flow cytometry, we studied bone marrow cells from 26 patients with MDS of all five FAB subtypes. The MMSA studied included Ia (HLA-DR), CD11b (Mo1), CD14 (Mo2, My4), CD13 (My7), and CD33 (My9). Marrows were considered "positive" for a given MMSA if the percentage of reactive cells exceeded the upper limit of the normal range. Twenty-four of twenty-six patients (92.3%) were CD13 (My7)+, suggesting that CD13 may serve as a diagnostic marker for MDS. Ten of twelve patients who developed ANLL during a median follow-up of 44 weeks were Ia(HLA-DR)+. The Kaplan-Meier estimated median time to leukemia (TTL) was 16 weeks for Ia+ patients and 88 weeks for Ia- patients (P = 0.004). All six patients who developed ANLL before 16 weeks from diagnosis were Ia+, while none of the Ia- patients converted to ANLL before 24 weeks. Nine of thirteen patients with low CD11b (Mo1) expression (< 53% reactive cells) developed ANLL, compared with only two of 11 patients with high CD11b expression (> 53% reactive cells). Kaplan-Meier estimated TTL was 29 weeks for patients with low CD11b, compared to 160 weeks for patients with high CD11b (P < 0.05). Patients who met both criteria, Ia+ and low CD11b, represented the poorest prognostic subgroup, with median TTL of 13 weeks compared with 88 weeks for the others (P = 0.017). Ia and CD11b patterns were not specific for MDS subtype, and their expression did not correlate with blast count. These data suggest that MDS patients whose bone marrow cells demonstrate high Ia (HLA-DR) and low CD11b (Mo1) expression represent a poor prognostic subgroup with short TTL. These patients may be candidates for early aggressive or investigational treatment.