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 Kornblau; Susan O'Brien; Sherry Pierce; Jeffrey Jorgensen; Kenna R. Mills Shaw; Cheryl L. Willman; Charles G. Mullighan; Hagop Kantarjian; Marina Konopleva

doi:10.1182/blood-2016-07-726588

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^*

^*Corresponding author for this work

Pathology

Research output: Contribution to journal › Article › peer-review

260 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 language	English (US)
Pages (from-to)	572-581
Number of pages	10
Journal	Blood
Volume	129
Issue number	5
DOIs	https://doi.org/10.1182/blood-2016-07-726588
State	Published - Feb 2 2017

Funding

This work was supported in part by Cancer Prevention and Research Institute of Texas Grant "Defining and Treating Targetable Lesions in AYA Acute Lymphoblastic Leukemia" (N.J. and M.K.), the American Lebanese Syrian Associated Charities of St. Jude Children's Research Hospital, Stand Up to Cancer Innovative Research Grant and St. Baldrick's Foundation Scholar Award (C.G.M.), American Society of Hematology Scholar Award (K.G.R.), and National Institutes of Health, National Cancer Institute Grants CA21765 (St. Jude Cancer Center Support Grant), HHSN261200800001E (C.G.M.), U01 CA157937 (C.L.W.) and CA157937 and CA118100 (UNM Comprehensive Cancer Center), and a Leukemia and Lymphoma Society Specialized Center of Research Grant (St. Jude and UNM Comprehensive Cancer Centers).

ASJC Scopus subject areas

Hematology
Biochemistry
Cell Biology
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1182/blood-2016-07-726588

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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

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title = "Ph-like acute lymphoblastic leukemia: A high-risk subtype in adults",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2017 by The American Society of Hematology.",

year = "2017",

month = feb,

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doi = "10.1182/blood-2016-07-726588",

language = "English (US)",

volume = "129",

pages = "572--581",

journal = "Blood",

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publisher = "American Society of Hematology",

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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

TY - JOUR

T1 - Ph-like acute lymphoblastic leukemia

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

Y1 - 2017/2/2

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.

AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=85014854171&partnerID=8YFLogxK

U2 - 10.1182/blood-2016-07-726588

DO - 10.1182/blood-2016-07-726588

M3 - Article

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AN - SCOPUS:85014854171

SN - 0006-4971

VL - 129

SP - 572

EP - 581

JO - Blood

JF - Blood

IS - 5

ER -

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

Abstract

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ASJC Scopus subject areas

UN SDGs

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