Prognostic significance of immunophenotypic and karyotypic features of Philadelphia positive B-lymphoblastic leukemia in the era of tyrosine kinase inhibitors

Jesse Jaso, Deborah A. Thomas, Krista Cunningham, Jeffrey L. Jorgensen, Hagop M. Kantarjian, L. Jeffrey Medeiros, Sa A. Wang

Research output: Contribution to journalArticle

31 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4009-4017
Number of pages9
JournalCancer
Volume117
Issue number17
DOIs
StatePublished - Sep 1 2011

Keywords

  • Philadelphia chromosome
  • acute lymphoblastic leukemia
  • immunophenotype
  • karyotype

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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