Determining the underlying cause of persistent eosinophilia is important for effective clinical management but remains a diagnostic challenge in many cases. We identified STAT5B N642H, an established oncogenic mutation, in 27/1715 (1.6%) cases referred for investigation of eosinophilia. Of the 27 mutated cases, a working diagnosis of hypereosinophilic syndrome (HES; n = 7) or a myeloid neoplasm with eosinophilia (n = 20) had been made prior to the detection of STAT5B N642H. Myeloid panel analysis identified a median of 2 additional mutated genes (range 0–4) with 4 cases having STAT5B N642H as a sole abnormality. STAT5B N642H was absent in cultured T cells of 4/4 positive cases. Individuals with SF3B1 mutations (9/27; 33%) or STAT5B N642H as a sole abnormality had a markedly better overall survival compared to cases with other additional mutations (median 65 months vs. 14 months; hazard ratio = 8.1; P < 0.001). The overall survival of STAT5B-mutated HES cases was only 30 months, suggesting that these cases should be reclassified as chronic eosinophilic leukemia, not otherwise specified (CEL-NOS). The finding of STAT5B N642H as a recurrent mutation in myeloid neoplasia with eosinophilia provides a new diagnostic and prognostic marker as well as a potential target for therapy.

Summary. Many solid tumours have been shown to lack expression of either of the immune co-stimulatory molecules CD80 (B7AE1) or CD86 (B7AE2), which is thought to be one of the ways in which tumours may escape immune recognition. We have examined the surface expression of CD80, CD86, human leucocyte antigen (HLA) class I and II, CD11a, CD54, and CD58 on the blast cells from patients with acute myeloid leukaemia (AML) at presentation. CD80 was only rarely expressed on AML blasts and, in those leukaemic cells expressing CD80, the level of expression was low. In contrast, expression of CD86 was detected on the AML blasts in more than half of the samples tested and, in some cases, the level of expression was equivalent to that of mature monocytes and activated B lymphocytes. The percentage of leukaemic blasts expressing CD86 was higher in the M4 and M5 French-American-British (FAB) types, and expression of CD11a and HLA class II was higher in the M4 FAB type. There was no difference in expression of CD80, CD54, CD58, or HLA Class I between different FAB subgroups. There was no significant difference in duration of first remission with expression of CD80, CD86, CD11a, CD54 or HLA class II. However, when expression of CD80 and CD86 were considered together, a significantly longer duration of remission was found. We suggest that these molecules may play a role in immunosurveillance, resulting in prolonged remission in some patients treated for AML.

AddressesBackground We investigated how sensitive serum free light chain (FLC) analysis was for the detection of Bence-Jones protein (BJP) and whether a serum k/l ratio could replace urine electrophoresis as part of the investigation algorithm for monoclonal gammopathy.

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