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

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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

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Protein-Tyrosine Kinases
CD13 Antigens
Chromosomes
Reverse Transcriptase Polymerase Chain Reaction
Fluorescence In Situ Hybridization
Drug Therapy
Oncogene Fusion
B-Lymphocytes
Interleukin-2 Receptor alpha Subunit
Philadelphia Chromosome
Genetic Heterogeneity
Phosphoproteins
Carcinoembryonic Antigen
Cell Adhesion Molecules
Diploidy
Molecular Biology
Leukemia
Multivariate Analysis
Antigens

Keywords

  • acute lymphoblastic leukemia
  • immunophenotype
  • karyotype
  • Philadelphia chromosome

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Prognostic significance of immunophenotypic and karyotypic features of Philadelphia positive B-lymphoblastic leukemia in the era of tyrosine kinase inhibitors. / Jaso, Jesse; Thomas, Deborah A.; Cunningham, Krista; Jorgensen, Jeffrey L.; Kantarjian, Hagop M.; Medeiros, L. Jeffrey; Wang, Sa A.

In: Cancer, Vol. 117, No. 17, 01.09.2011, p. 4009-4017.

Research output: Contribution to journalArticle

Jaso, Jesse ; Thomas, Deborah A. ; Cunningham, Krista ; Jorgensen, Jeffrey L. ; Kantarjian, Hagop M. ; Medeiros, L. Jeffrey ; Wang, Sa A. / Prognostic significance of immunophenotypic and karyotypic features of Philadelphia positive B-lymphoblastic leukemia in the era of tyrosine kinase inhibitors. In: Cancer. 2011 ; Vol. 117, No. 17. pp. 4009-4017.
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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.",
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T1 - Prognostic significance of immunophenotypic and karyotypic features of Philadelphia positive B-lymphoblastic leukemia in the era of tyrosine kinase inhibitors

AU - Jaso, Jesse

AU - Thomas, Deborah A.

AU - Cunningham, Krista

AU - Jorgensen, Jeffrey L.

AU - Kantarjian, Hagop M.

AU - Medeiros, L. Jeffrey

AU - Wang, Sa A.

PY - 2011/9/1

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N2 - 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.

AB - 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.

KW - acute lymphoblastic leukemia

KW - immunophenotype

KW - karyotype

KW - Philadelphia chromosome

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