The curative potential of hematopoietic cell transplantation in the treatment of acute myeloid leukemia (AML) suggests that the immune system is involved in the disease outcome. One of the major obstacles in the development of immunotherapeutic protocols is the lack of specific antigens. Mutations in NPM1 gene are characteristic for AML, they are found in about a third of AML patients and are relatively stable during the disease course. Patients with these mutations form a specific group with better prognosis which might be associated with an immune response against the mutated protein or against its interaction partners.
We evaluated a set of known markers of immune suppression in a cohort of 30 AML patients at diagnosis, with special focus on possible differences between patients with wild-type and mutated NPM1 (NPMwt versus NPMmut). Positive cell fraction and the mean expression levels were determined for each marker using flow cytometry. NPM1 mutations were detected by PCR and by immunofluorescence (cytoplasmic signal).
We found decreased HLA class I expression in a subgroup of NPMmut, but not in NPMwt group. Independently of NPM1 mutations, a part of patients had increased expression of PD-L1, CLIP or Tim-3. These markers were partly mutually correlated. We have also detected increased expression of CD47 and decreased expression of HLA-DR on leukemia blasts in NPMmut group compared to NPMwt. Furthermore, NPMmut patients had higher percentage of CD27-positive B-cells. On the other hand, no difference between NPMmut and NPMwt were found on T-lymphocytes.
Our results confirm that patients with mutated NPM1 form an immunologically specific AML subgroup with increased markers of immune suppression at diagnosis.
Institute of Hematology and Blood Transfusion.
Ministry of Health of the Czech Republic (grant No 16-30268A).
All authors have declared no conflicts of interest.