TY - JOUR
T1 - CD36-positive B-lymphoblasts predict poor outcome in children with B-lymphoblastic leukemia
AU - Newton, Joanna G.
AU - Horan, John T.
AU - Newman, Scott
AU - Rossi, Michael R.
AU - Ketterling, Rhett P.
AU - Park, Sunita I.
N1 - Funding Information:
The results published here are in part based upon data generated by the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative managed by the NCI. The data used for this analysis are available with dbGAP accession number phs000464. Information about TARGET can be found at http://ocg.cancer.gov/programs/target. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Research reported in this publication was supported in part by the Biostatistics and Bioinformatics Shared resource of Winship Cancer Institute of Emory University and NIH/NCI under award number P30CA138292. This research was also supported by the Children’s Healthcare of Atlanta Vision Endowment fund.
Publisher Copyright:
© 2017, Society for Pediatric Pathology All rights reserved.
PY - 2017/6
Y1 - 2017/6
N2 - Objective: We observed that pediatric patients with B lymphoblastic leukemia which expressed CD36 at diagnosis seemed to have worse outcome than patients whose blasts did not. Here, we describe the patient, disease characteristics, pathological, molecular, and genetic features and outcomes of patients with CD36þ B-LL compared to patients with CD36 B-LL. Methods: We retrospectively reviewed all flow cytometry reports from September 2008 to December 2015 to identify patients diagnosed at our institution with CD36 expression on B lymphoblasts. CD36 control patients were chosen from our leukemia database and matched 2:1 to CD36þ patients for National Cancer Institute (NCI) risk group at diagnosis. We reviewed diagnostic marrow slides for cytoplasmic granules and abstracted clinical data from patient charts. To identify underlying genetic abnormalities, clinical FISH testing and RNA sequencing was performed on 5 of our CD36þ patients, and RNA-seq data from the NIH Therapeutically Applicable Research to Generate Effective Treatments (TARGET) ALL Expansion Phase 2 data set were examined. Results: Twenty-five of 366 (6.83%) patients diagnosed at our institution in the study period had CD36þ blasts. With a median follow-up of 5.32 years, 5-year event-free survival (EFS) and overall survival (OS) were significantly worse for CD36þ patients compared to CD36 patients who were NCI Standard Risk at diagnosis (EFS: 60% 15.49 vs 95% 4.87, P ¼.016; OS: 90% 9.5 vs 100%, P ¼.019). NCI Standard Risk patients whose blasts were both CD36þ and had granules had the worst survival compared to CD36 patients without granules (EFS 25% 21.65 vs 95% 4.87, P ¼.0004). From our CD36þ patients and the TARGET database, we found 2 ABL2 mutations, 1 PDGFRB mutation, and 2 NRAS mutations. Conclusions: For NCI Standard Risk patients, CD36 expression on B-lymphoblasts identifies patients with B-LL who have especially poor outcome. This may be due to underlying genetic abnormalities that may be amenable to targeted therapy.
AB - Objective: We observed that pediatric patients with B lymphoblastic leukemia which expressed CD36 at diagnosis seemed to have worse outcome than patients whose blasts did not. Here, we describe the patient, disease characteristics, pathological, molecular, and genetic features and outcomes of patients with CD36þ B-LL compared to patients with CD36 B-LL. Methods: We retrospectively reviewed all flow cytometry reports from September 2008 to December 2015 to identify patients diagnosed at our institution with CD36 expression on B lymphoblasts. CD36 control patients were chosen from our leukemia database and matched 2:1 to CD36þ patients for National Cancer Institute (NCI) risk group at diagnosis. We reviewed diagnostic marrow slides for cytoplasmic granules and abstracted clinical data from patient charts. To identify underlying genetic abnormalities, clinical FISH testing and RNA sequencing was performed on 5 of our CD36þ patients, and RNA-seq data from the NIH Therapeutically Applicable Research to Generate Effective Treatments (TARGET) ALL Expansion Phase 2 data set were examined. Results: Twenty-five of 366 (6.83%) patients diagnosed at our institution in the study period had CD36þ blasts. With a median follow-up of 5.32 years, 5-year event-free survival (EFS) and overall survival (OS) were significantly worse for CD36þ patients compared to CD36 patients who were NCI Standard Risk at diagnosis (EFS: 60% 15.49 vs 95% 4.87, P ¼.016; OS: 90% 9.5 vs 100%, P ¼.019). NCI Standard Risk patients whose blasts were both CD36þ and had granules had the worst survival compared to CD36 patients without granules (EFS 25% 21.65 vs 95% 4.87, P ¼.0004). From our CD36þ patients and the TARGET database, we found 2 ABL2 mutations, 1 PDGFRB mutation, and 2 NRAS mutations. Conclusions: For NCI Standard Risk patients, CD36 expression on B-lymphoblasts identifies patients with B-LL who have especially poor outcome. This may be due to underlying genetic abnormalities that may be amenable to targeted therapy.
KW - B-lymphoblastic leukemia
KW - CD36
KW - Outcome
KW - Predictor
KW - Prognosis
KW - Risk factor
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U2 - 10.1177/1093526616688753
DO - 10.1177/1093526616688753
M3 - Article
AN - SCOPUS:85027098654
SN - 1093-5266
VL - 20
SP - 224
EP - 231
JO - Pediatric and Developmental Pathology
JF - Pediatric and Developmental Pathology
IS - 3
ER -