Malignancies of natural killer (NK) cell precursor: myeloid/NK cell precursor acute leukemia and blastic NK cell lymphoma/leukemia.

Malignant hematolymphoid disorders arising from natural killer (NK) cells have become widely recognized in the past decade. Recently, we as well as others have drawn attention to some neoplasms of conceivable NK cell precursor origin that might represent two distinct entities, i.e. myeloid/NK cell precursor acute leukemia and blastic NK cell lymphoma/leukemia. Both of these diseases were characterized by remarkable extramedullary involvement and lymphoblastoid morphology, although the sites of involvement differed. Myeloid/NK cell precursor acute leukemia exhibited more frequent involvement of bone marrow (BM) and lymph nodes, whereas blastic NK cell lymphoma/leukemia affected extranodal sites, mainly the skin/subcutis. Tumor cells of these two diseases shared the CD16-, CD56+ and CD57- phenotype, but differed in other phenotypic profiles. Indeed, myeloid/NK cell precursor acute leukemia was immunophenotypically characterized by the expression of CD34 and blastic NK cell lymphoma/leukemia by that of CD4. On the theoretical level in the NK cell differentiation pathway, myeloid/NK cell precursor acute leukemia might be derived from a myeloid antigen-positive precursor preceding a NK cell committed precursor as a conceivable counterpart of blastic NK cell lymphoma/leukemia. Most cases with either disease lacked cytotoxic activities or molecules, a finding which seems to support their precursor origin. Notably, Epstein Barr virus (EBV) was negative in all cases, which contrasted with its high level associated with mature NK cell malignancies. Chemotherapy for acute myeloid leukemia was generally effective for myeloid/NK cell precursor acute leukemia, while the regimen for lymphoid malignancy was effective for blastic NK cell lymphoma/leukemia. These data suggests that each of these two diseases constitutes a distinct entity, which is also different from mature NK cell malignancies.