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.
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Nitin
authors.initials: N
authors.lastname: Jain
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN.
authors.forename: Kathryn G
authors.initials: KG
authors.lastname: Roberts
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.affiliation: Department of Hematopathology.
authors.forename: Keyur
authors.initials: K
authors.lastname: Patel
authors.affiliation: Institute for Personalized Cancer Therapy, and.
authors.forename: Agda Karina
authors.initials: AK
authors.lastname: Eterovic
authors.affiliation: Institute for Personalized Cancer Therapy, and.
authors.forename: Ken
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Patrick
authors.initials: P
authors.lastname: Zweidler-McKay
authors.affiliation: Department of Hematopathology.
authors.forename: Xinyan
authors.initials: X
authors.lastname: Lu
authors.affiliation: Institute for Personalized Cancer Therapy, and.
authors.forename: Gloria
authors.initials: G
authors.lastname: Fawcett
authors.affiliation: Department of Hematopathology.
authors.forename: Sa A
authors.initials: SA
authors.lastname: Wang
authors.affiliation: Department of Hematopathology.
authors.forename: Sergej
authors.initials: S
authors.lastname: Konoplev
authors.affiliation: Department of Pathology, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM; and.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Harvey
authors.affiliation: Department of Pathology, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM; and.
authors.forename: I-Ming
authors.initials: IM
authors.lastname: Chen
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN.
authors.forename: Debbie
authors.initials: D
authors.lastname: Payne-Turner
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN.
authors.forename: Marcus
authors.initials: M
authors.lastname: Valentine
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Steven
authors.initials: S
authors.lastname: Kornblau
authors.affiliation: Division of Hematology/Oncology, Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, CA.
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.affiliation: Department of Hematopathology.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Jorgensen
authors.affiliation: Institute for Personalized Cancer Therapy, and.
authors.forename: Kenna R Mills
authors.initials: KR
authors.lastname: Shaw
authors.affiliation: Department of Pathology, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM; and.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Willman
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN.
authors.forename: Charles G
authors.initials: CG
authors.lastname: Mullighan
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Marina
authors.initials: M
authors.lastname: Konopleva
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics*; D016016:Proportional Hazards Models; D018121:Receptors, Cytokine / Q000235:genetics; D012307:Risk Factors; D059467:Transcriptome; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; C498762:CRLF2 protein, human; D018121:Receptors, Cytokine; C507924:JAK2 protein, human; D053614:Janus Kinase 2