title: Molecular characteristics and chromatin texture features in acute promyelocytic leukemia.
abstract: BACKGROUND
  Acute promyelocytic leukemia is a cytogenetically well defined entity. Nevertheless, some features observed at diagnosis are related to a worse outcome of the patients.
  
  
  METHODS
  In 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.
  
  
  RESULTS
  Among 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.
  
  
  CONCLUSIONS
  in 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.
authors: State University of Campinas, Campinas, Brazil.
authors: Mariana R B
authors: MR
authors: De Mello
authors: Dulcineia M
authors: DM
authors: Albuquerque
authors: Fernanda Gonçalves
authors: FG
authors: Pereira-Cunha
authors: Krizzia B
authors: KB
authors: Albanez
authors: Katia B B
authors: KB
authors: Pagnano
authors: Fernando F
authors: FF
authors: Costa
authors: Konradin
authors: K
authors: Metze
authors: Irene
authors: I
authors: Lorand-Metze
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D002843:Chromatin / Q000648:ultrastructure*; D042002:Chromatin Assembly and Disassembly; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D017709:Fractals; D006801:Humans; D016130:Immunophenotyping; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C493966:CDKN2B protein, human; D002843:Chromatin; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3