title: Minimal residual disease in acute myelogenous leukemia with PML/RAR alpha or AML1/ETO mRNA and phenotypic analysis of possible T and natural killer cells in bone marrow.
abstract: Here we studied minimal residual disease (MRD) of patients with acute myeloid leukemia (AML) who have PML/RAR alpha or AML1/ETO as well as the phenotypic analysis of lymphocyte subsets involved in antitumor immunity. Eight patients in long-term (LT; 3 to 15 years) and 15 patients in short-term (ST; up to 3 years) remission were studied. Using the reverse transcription-polymerase chain reaction (RT) assay, the limit of detection was 10(-5) to 10(-6) for PML/RAR alpha transcript and 10(-4) to 10(-5) for the AML1/ETO transcript. Simultaneously, T lymphocyte subsets and NK cells from the peripheral blood (PB) and bone marrow (BM) were investigated by flow cytometric analysis. Four of the eight patients in LT and 7 of the 15 patients in ST remission were MRD-positive. Although all MRD-positive patients in LT remission are still until now event-free, 3 of the 7 MRD-positive (MRD+) patients in ST remission soon relapsed. The total populations of CD4+, CD8+ and CD56+ [possible T-cell and natural killer (T/NK) populations] in the BM of ST patients and MRD+/LT patients were significantly (p < .01) low. The CD8+ CD28+ population showed the same tendency (p < .01-.02). The T/NK subsets in the BM of MRD-negative (MRD-) LT (MRD-/LT) patients showed similar numbers of cells as normal volunteers. Basically, the total percentage of the CD4+, CD8+ and CD56+ cell populations in the BM was increased and in the following order: MRD-/LT patients, normal volunteers, MRD+/LT patients and MRD+ or -/ST patients. The percentages of the T/NK-cell subsets in the PB were not significantly different among these groups. Thus, the difference of the possible T/NK-cell phenotype in the BM may strongly influence clinical and molecular remission. These results still remain to be confirmed by further studies of the functional anti-tumor immunity of T/NK cells of AML in remission.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Inokuchi
authors.forename: R
authors.initials: R
authors.lastname: Iwakiri
authors.forename: M
authors.initials: M
authors.lastname: Futaki
authors.forename: H
authors.initials: H
authors.lastname: Hanawa
authors.forename: S
authors.initials: S
authors.lastname: Tanosaki
authors.forename: T
authors.initials: T
authors.lastname: Nomura
authors.forename: K
authors.initials: K
authors.lastname: Dan
mesh_terms: D050676:Core Binding Factor Alpha 2 Subunit; D004273:DNA, Neoplasm / Q000032:analysis; D018572:Disease-Free Survival; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000473:pathology*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D018365:Neoplasm, Residual; D015514:Oncogene Proteins, Fusion / Q000032:analysis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D000075142:RUNX1 Translocation Partner 1 Protein; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000235:genetics; D012074:Remission Induction; D016176:T-Lymphocyte Subsets / Q000473:pathology*; D013997:Time Factors; D014157:Transcription Factors / Q000032:analysis* / Q000235:genetics
chemical_list: C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein