title: Prognostic significance of immunophenotypic and karyotypic features of Philadelphia positive B-lymphoblastic leukemia in the era of tyrosine kinase inhibitors.
abstract: BACKGROUND
  Philadelphia chromosome (Ph)-positive B-lymphoblastic leukemia exhibits immunophenotypic, karyotypic, and molecular genetic heterogeneity. The prognostic significance of these parameters was assessed in the context of intensive tyrosine kinase inhibitor (TKI)-based chemotherapy.
  
  
  METHODS
  The authors studied 65 adult patients with Ph-positive acute lymphoblastic leukemia (ALL) who received treatment with TKI-based therapy, correlated their clinicopathologic heterogeneity with patient outcome, and compared the findings with those from 60 adult patients with diploid B-cell ALL who received similar chemotherapy without a TKI.
  
  
  RESULTS
  Ph-positive ALL was associated with older age (P = .01), the common-B immunophenotype characterized by a greater frequency of CD13 (alanine aminopeptidase) coexpression (P = .004), CD66c (carcinoembryonic antigen-related cell adhesion molecule 3) expression (P = .007), and CD25 (interleukin-2 receptor alpha chain) expression (P < .001) and with a lower frequency of CD15 (3-fucosyl-N-acetyl-lactosamine) expression (P < .001). Conventional karyotypic analyses indicated that the Ph chromosome was the sole abnormality in 19 patients (30%), was present with other aberrancies in 43 patients (65%), and was absent (detectable only by fluorescence in situ hybridization [FISH] or quantitative reverse transcriptase-polymerase chain reaction [RT-PCR] analysis) in 3 patients (5%). The presence of the breakpoint cluster region-v-Abelson murine leukemia viral oncogene homolog fusion gene (BCR-ABL) was confirmed in all patients by FISH or RT-PCR (the 190-kDa protein [p190] construct was present in 49 patients [77%], and the p210 fusion transcript construct was present in 15 patients [23%]). The presence of a supernumerary Ph chromosome was correlated with a higher incidence of CD20 (B-lymphocyte antigen, nonglycosylated phosphoprotein) expression (P < .001), whereas the p210 construct was correlated with aberrant CD25 expression (P = .05). Outcomes were not influenced by the degree of karyotypic complexity (including the presence or absence of a supernumerary Ph chromosome), CD20 expression, or myeloid antigen expression (CD13, CD33 [myeloid lineage transmembrane receptor], CD66c). CD25 expression was associated with inferior survival in univariate analysis (P = .051) but not in multivariate analysis (P = .092).
  
  
  CONCLUSIONS
  In the context of intensive, TKI-based chemotherapy, the immunophenotypic, karyotypic, and molecular heterogeneity of Ph-positive ALL no longer influences outcome.
authors.affiliation: Department of Pathology, The University of Texas Medical Center Health Sciences Center, Houston, Texas, USA.
authors.forename: Jesse
authors.initials: J
authors.lastname: Jaso
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Thomas
authors.forename: Krista
authors.initials: K
authors.lastname: Cunningham
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Jorgensen
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: Sa A
authors.initials: SA
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002869:Chromosome Aberrations; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000276:immunology*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors