摘要 :
Summary Cell cycle status may play an important role in directing patient therapy. We therefore determined the cell cycle status of leukaemic cells by immunophenotypic analysis of bone marrow trephine biopsies from 181 patients wi...
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Summary Cell cycle status may play an important role in directing patient therapy. We therefore determined the cell cycle status of leukaemic cells by immunophenotypic analysis of bone marrow trephine biopsies from 181 patients with acute myeloid leukaemia ( AML ) and correlated the results with biological features and clinical outcome. There was considerable heterogeneity between patients. The presenting white cell count significantly correlated with the proportion of non‐quiescent cells ( P? < ? 0·0001), of cycling cells beyond G 1 ( P? < ? 0·0001) and the speed of cycling ( P? < ? 0·0001). Profiles in acute promyelocytic leukaemia ( APL ) differed from non‐ APL and were consistent with more differentiated cells with reduced proliferative potential, but no significant differences were observed between non‐ APL cytogenetic risk groups. NPM 1 mutations but not FLT 3 internal tandem duplication ( FLT 3 ITD ) were significantly associated with a higher proportion of cells beyond G 1 ( P? = ? 0·002) and faster speed of cycling ( P? = ? 0·003). Resistance to standard cytosine arabinoside and daunorubicin induction chemotherapy was significantly related to a slower speed of cycling ( P? = ? 0·0002), as was a higher relapse rate ( P? = ? 0·05), but not with the proportion of non‐quiescent cells or actively cycling cells. These results show a link between the cycling speed of AML cells and the response to chemotherapy, and help to identify a group with a very poor prognosis.
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摘要 :
Summary Although an NPM1 mutation is generally considered to be a good prognostic marker in acute myeloid leukaemia, it has recently been suggested that a higher level of NPM1 mutant ( NPM1 MUT ) alleles relative to wild‐type all...
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Summary Although an NPM1 mutation is generally considered to be a good prognostic marker in acute myeloid leukaemia, it has recently been suggested that a higher level of NPM1 mutant ( NPM1 MUT ) alleles relative to wild‐type alleles is associated with poor clinical outcome. We therefore sought to confirm this finding in a larger study of 876 NPM1 MUT cases entered into UK national trials. In univariate analysis, the higher NPM1 MUT allele burden was associated with a lower complete remission (CR) rate, higher relapse rate and reduced overall survival, but this was largely attributable to the association of the higher NPM1 MUT allele burden with other known poor risk factors, particularly the presence of a concomitant FLT3 internal tandem duplication. In multivariate analysis, there was no significant impact of the NPM1 MUT allele burden on CR rates, and the impact on relapse and overall survival, whilst still significant, was greatly reduced. This impact was similar in patients who did or did not receive an allogeneic transplant in first CR. We conclude that the binary presence or absence of an NPM1 mutation, combined with minimal residual disease levels following induction therapy, should continue to be used in therapeutic management rather than stratification according to the NPM1 MUT level.
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