Abstract
BackgroundAcute promyelocytic leukemia is a cytogenetically well defined entity. Nevertheless, some features observed at diagnosis are related to a worse outcome of the patients.MethodsIn a prospective study, we analyzed peripheral (PB) leukocyte count, immunophenotype, methylation status of CDKN2B, CDKN2A and TP73; FLT3 and NPM1 mutations besides nuclear chromatin texture characteristics of the leukemic cells. We also examined the relation of these features with patient’s outcome.ResultsAmong 19 cases, 4 had a microgranular morphology, 7 presented PB leukocytes >10x109/l, 2 had FLT3-ITD and 3 had FLT3-TKD (all three presenting a methylated CDKN2B). NPM1 mutation was not observed. PB leukocyte count showed an inverse relation with standard deviation of gray levels, contrast, cluster prominence, and chromatin fractal dimension (FD). Cases with FLT3-ITD presented a microgranular morphology, PB leukocytosis and expression of HLA-DR, CD34 and CD11b. Concerning nuclear chromatin texture variables, these cases had a lower entropy, contrast, cluster prominence and FD, but higher local homogeneity, and R245, in keeping with more homogeneously distributed chromatin. In the univariate Cox analysis, a higher leukocyte count, FLT3-ITD mutation, microgranular morphology, methylation of CDKN2B, besides a higher local homogeneity of nuclear chromatin, a lower chromatin entropy and FD were associated to a worse outcome. All these features lost significance when the cases were stratified for FLT3-ITD mutation. Methylation status of CDNK2A and TP73 showed no relation to patient’s survival.Conclusionin APL, patients with FLT3-ITD mutation show different clinical characteristics and have blasts with a more homogeneous chromatin texture. Texture analysis demonstrated that FLTD-ITD was accompanied not only by different cytoplasmic features, but also by a change in chromatin structure in routine cytologic preparations. Yet we were not able to detect chromatin changes by nuclear texture analysis of patients with the FTLD-TKD or methylation of specific genes.
Highlights
Acute promyelocytic leukemia is a cytogenetically well defined entity
In Brazil, Acute promyelocytic leukemia (APL) accounts for about 20% of the adult patients with de novo acute myeloid leukemia (AML), which is a higher proportion than what is found in USA or Europe [1,2,3,4,5,6,7]
The disease is a cytogenetically clearly defined entity, several clinical and biological features have shown to be of prognostic importance, such as presence of the so-called variant morphology of the leukemic cells, high peripheral leukocyte counts at diagnosis or different RARα fusion partners [1,2,3]
Summary
Acute promyelocytic leukemia is a cytogenetically well defined entity. some features observed at diagnosis are related to a worse outcome of the patients. Acute promyelocytic leukemia (APL) is a well characterized subtype of acute myeloid leukemia (AML) defined by a specific cytogenetic alteration of the tyrosine kinase 3 gene [1,2,3,4,5]. The disease is a cytogenetically clearly defined entity, several clinical and biological features have shown to be of prognostic importance, such as presence of the so-called variant (microgranular) morphology of the leukemic cells, high peripheral leukocyte counts at diagnosis or different RARα fusion partners [1,2,3]. Whereas in other AML subtypes, cytogenetic alterations and specific gene mutations are relevant for patients’ outcome, the prognostic relevance of additional karyotype abnormalities or gene mutations in APL patients are still controversial [1,2,3,6,7]
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