Ph-like acute lymphoblastic leukemia: A high-risk subtype in adults

Nitin Jain, Kathryn G. Roberts, Elias Jabbour, Keyur Patel, Agda Karina Eterovic, Ken Chen, Patrick Zweidler-McKay, Xinyan Lu, Gloria Fawcett, Sa A. Wang, Sergej Konoplev, Richard C. Harvey, I. Ming Chen, Debbie Payne-Turner, Marcus Valentine, Deborah Thomas, Guillermo Garcia-Manero, Farhad Ravandi, Jorge Cortes, Steven KornblauSusan O'Brien, Sherry Pierce, Jeffrey Jorgensen, Kenna R. Mills Shaw, Cheryl L. Willman, Charles G. Mullighan, Hagop Kantarjian, Marina Konopleva

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL) is a high-risk subtype of ALL in children. There are conflicting data on the incidence and prognosis of Ph-like ALL in adults. Patients with newly diagnosed B-cell ALL (B-ALL) who received frontline chemotherapy at MD Anderson Cancer Center underwent gene expression profiling of leukemic cells. Of 148 patients, 33.1% had Ph-like, 31.1% had Ph+, and 35.8% had other B-ALL subtypes (B-other). Within the Ph-like ALL cohort, 61% had cytokine receptor-like factor 2 (CRLF2) overexpression. Patients with Ph-like ALL had significantly worse overall survival (OS), and event-free survival compared with B-other with a 5-year survival of 23% (vs 59% for B-other, P = .006). Sixty-eight percent of patients with Ph-like ALL were of Hispanic ethnicity. The following were associated with inferior OS on multivariable analysis: age (hazard ratio [HR], 3.299; P < .001), white blood cell count (HR, 1.910; P = .017), platelet count (HR, 7.437; P = .005), and Ph-like ALL (HR, 1.818; P = .03). Next-generation sequencing of the CRLF2+ group identified mutations in the JAK-STAT and Ras pathway in 85% of patients, and 20% had a CRLF2 mutation. Within the CRLF2+ group, JAK2 mutation was associated with inferior outcomes. Our findings show high frequency of Ph-like ALL in adults, an increased frequency of Ph-like ALL in adults of Hispanic ethnicity, significantly inferior outcomes of adult patients with Ph-like ALL, and significantly worse outcomes in the CRLF2+ subset of Ph-like ALL. Novel strategies are needed to improve the outcome of these patients.

Original languageEnglish (US)
Pages (from-to)572-581
Number of pages10
JournalBlood
Volume129
Issue number5
DOIs
StatePublished - Feb 2 2017

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Jain, N., Roberts, K. G., Jabbour, E., Patel, K., Eterovic, A. K., Chen, K., Zweidler-McKay, P., Lu, X., Fawcett, G., Wang, S. A., Konoplev, S., Harvey, R. C., Chen, I. M., Payne-Turner, D., Valentine, M., Thomas, D., Garcia-Manero, G., Ravandi, F., Cortes, J., ... Konopleva, M. (2017). Ph-like acute lymphoblastic leukemia: A high-risk subtype in adults. Blood, 129(5), 572-581. https://doi.org/10.1182/blood-2016-07-726588