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

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
Externally publishedYes

Fingerprint

Cytokine Receptors
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hazards
Cells
Chemotherapy
Chromosomes
Platelets
Gene expression
Hispanic Americans
Blood
Mutation
Survival
B-Lymphocytes
Philadelphia Chromosome
Gene Expression Profiling
Platelet Count
Leukocyte Count
Disease-Free Survival

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Jain, N., Roberts, K. G., Jabbour, E., Patel, K., Eterovic, A. K., Chen, K., ... 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

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

In: Blood, Vol. 129, No. 5, 02.02.2017, p. 572-581.

Research output: Contribution to journalArticle

Jain, N, Roberts, KG, Jabbour, E, Patel, K, Eterovic, AK, Chen, K, Zweidler-McKay, P, Lu, X, Fawcett, G, Wang, SA, Konoplev, S, Harvey, RC, Chen, IM, Payne-Turner, D, Valentine, M, Thomas, D, Garcia-Manero, G, Ravandi, F, Cortes, J, Kornblau, S, O'Brien, S, Pierce, S, Jorgensen, J, Mills Shaw, KR, Willman, CL, Mullighan, CG, Kantarjian, H & Konopleva, M 2017, 'Ph-like acute lymphoblastic leukemia: A high-risk subtype in adults', Blood, vol. 129, no. 5, pp. 572-581. https://doi.org/10.1182/blood-2016-07-726588
Jain N, Roberts KG, Jabbour E, Patel K, Eterovic AK, Chen K et al. Ph-like acute lymphoblastic leukemia: A high-risk subtype in adults. Blood. 2017 Feb 2;129(5):572-581. https://doi.org/10.1182/blood-2016-07-726588
Jain, Nitin ; Roberts, Kathryn G. ; Jabbour, Elias ; Patel, Keyur ; Eterovic, Agda Karina ; Chen, Ken ; Zweidler-McKay, Patrick ; Lu, Xinyan ; Fawcett, Gloria ; Wang, Sa A. ; Konoplev, Sergej ; Harvey, Richard C. ; Chen, I. Ming ; Payne-Turner, Debbie ; Valentine, Marcus ; Thomas, Deborah ; Garcia-Manero, Guillermo ; Ravandi, Farhad ; Cortes, Jorge ; Kornblau, Steven ; O'Brien, Susan ; Pierce, Sherry ; Jorgensen, Jeffrey ; Mills Shaw, Kenna R. ; Willman, Cheryl L. ; Mullighan, Charles G. ; Kantarjian, Hagop ; Konopleva, Marina. / Ph-like acute lymphoblastic leukemia : A high-risk subtype in adults. In: Blood. 2017 ; Vol. 129, No. 5. pp. 572-581.
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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.",
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T2 - A high-risk subtype in adults

AU - Jain, Nitin

AU - Roberts, Kathryn G.

AU - Jabbour, Elias

AU - Patel, Keyur

AU - Eterovic, Agda Karina

AU - Chen, Ken

AU - Zweidler-McKay, Patrick

AU - Lu, Xinyan

AU - Fawcett, Gloria

AU - Wang, Sa A.

AU - Konoplev, Sergej

AU - Harvey, Richard C.

AU - Chen, I. Ming

AU - Payne-Turner, Debbie

AU - Valentine, Marcus

AU - Thomas, Deborah

AU - Garcia-Manero, Guillermo

AU - Ravandi, Farhad

AU - Cortes, Jorge

AU - Kornblau, Steven

AU - O'Brien, Susan

AU - Pierce, Sherry

AU - Jorgensen, Jeffrey

AU - Mills Shaw, Kenna R.

AU - Willman, Cheryl L.

AU - Mullighan, Charles G.

AU - Kantarjian, Hagop

AU - Konopleva, Marina

PY - 2017/2/2

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N2 - 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.

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