Here, we propose that a molecularly distinct subtype of acute leukaemia with shared myeloid and T cell lymphoblastic features, which we term acute myeloid/T-lymphoblastic leukaemia (AMTL), is divided across 3 diagnostic categories owing to variable expression of markers deemed to be defining of myeloid and T-lymphoid lineages, such as myeloperoxidase and CD3.
Besides myeloperoxidase (MPO), which was used as the gold standard in differentiating AML from other type of ALs, the most specific markers for AML in our study were CD14 and CD64 (99.5 and 95.6%).
We established three sister cell lines, NALM-30, NALM-31 and NALM-32, with biphenotypic features carrying myeloperoxidase mRNA and protein with complex Philadelphia (Ph) chromosome, t(9;22;10)(q34;q11;q22), from a patient with Ph-positive acute leukemia in relapse.
A novel human leukemia cell line (Kasumi-3) was established from the blast cells of a 57-year-old man suffering from myeloperoxidase-negative acute leukemia.
MPO enzyme activity as determined by light microscopic cytochemistry has long been an important marker used in the diagnosis of acute leukemias and other hematopoietic disorders.
We have studied immunological features of 200 cases of acute leukemia (109 acute myelogenous leukemia, AML, and 91 acute lymphoblastic leukemia, ALL, according to FAB criteria), including 17 (8.5%) classified as biphenotypic by a scoring system based on the number and specificity of unexpected lineage antigens and which gives more weight to cytoplasmic markers such as myeloperoxidase, CD3, and CD22, and less to other membrane markers.
To determine if mutations in this putatively regulatory region of the MPO gene might be responsible for some of the differences in level of MPO expression among different cases or classes of acute leukemia, we compared the nucleotide sequence of this part of the gene from 16 patients with acute leukemia, with DNA from normal human bone marrow cells and selected other neoplasms and cell lines.
We conclude by showing that ISH can detect MPO mRNA in myeloblasts of patients with acute leukemia and can be a potentially useful technique in the study of myeloid differentiation in acute leukemias.
These results indicate that MPO gene expression may serve as an additional marker for subclassification of acute leukemias and may be used to identify leukemic cells arrested at an early stage of the myeloid differentiation pathway.