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Mutational profiling of acute lymphoblastic leukemia with testicular relapse. (J Hematol Oncol, Mar 2017)

Ding LW1, Sun QY2, Mayakonda A2, Tan KT2, Chien W2,3, Lin DC2,3, Jiang YY2, Xu L2, Garg M2,4, Lao ZT2,5, Lill M3, Yang H2, Yeoh AE6,7, Koeffler HP2,3.

1 Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
2 Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
3 Division of Hematology/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, USA.
4 Department of Medical Oncology and Clinical Research, Cancer Institute (WIA), Adyar Chennai, India.
5 Department of Haematology, Singapore General Hospital, Singapore, Singapore.
6 Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
7 Department of Pediatrics, Division of Hematology and Oncology, National University Health System, Singapore, Singapore.

Abstract
Relapsed acute lymphoblastic leukemia (ALL) is the leading cause of deaths of childhood cancer. Although relapse usually happens in the bone marrow, extramedullary relapse occasionally occurs including either the central nervous system or testis (<1-2%). We selected two pediatric ALL patients who experienced testicular relapse and interrogated their leukemic cells with exome sequencing. The sequencing results and clonality analyses suggest that relapse of patient D483 directly evolved from the leukemic clone at diagnosis which survived chemotherapy. In contrast, relapse leukemia cells (both bone marrow and testis) of patient D727 were likely derived from a common ancestral clone, and testicular relapse likely arose independently from the bone marrow relapsed leukemia. Our findings decipher the mutational spectra and shed light on the clonal evolution of two cases of pediatric ALL with testicular relapse. Presence of CREBBP/NT5C2 mutations suggests that a personalized therapeutic approach should be applied to these two patients.

KEYWORDS: ALL; Acute lymphoblastic leukemia; Extramedullary relapse; Testicular relapse

PMID: 28253933