TY - JOUR
T1 - High Frequency and Poor Outcome of Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia in Adults
AU - Roberts, Kathryn G.
AU - Gu, Zhaohui
AU - Payne-Turner, Debbie
AU - McCastlain, Kelly
AU - Harvey, Richard C.
AU - Chen, I. Ming
AU - Pei, Deqing
AU - Iacobucci, Ilaria
AU - Valentine, Marcus
AU - Pounds, Stanley B.
AU - Shi, Lei
AU - Li, Yongjin
AU - Zhang, Jinghui
AU - Cheng, Cheng
AU - Rambaldi, Alessandro
AU - Tosi, Manuela
AU - Spinelli, Orietta
AU - Radich, Jerald P.
AU - Minden, Mark D.
AU - Rowe, Jacob M.
AU - Luger, Selina
AU - Litzow, Mark R.
AU - Tallman, Martin S.
AU - Wiernik, Peter H.
AU - Bhatia, Ravi
AU - Aldoss, Ibrahim
AU - Kohlschmidt, Jessica
AU - Mrózek, Krzysztof
AU - Marcucci, Guido
AU - Bloomfield, Clara D.
AU - Stock, Wendy
AU - Kornblau, Stephen
AU - Kantarjian, Hagop M.
AU - Konopleva, Marina
AU - Paietta, Elisabeth
AU - Willman, Cheryl L.
AU - Mullighan, Charles G.
PY - 2017/2/1
Y1 - 2017/2/1
N2 - Purpose Philadelphia chromosome (Ph) -like acute lymphoblastic leukemia (ALL) is a high-risk subtype of childhood ALL characterized by kinase-activating alterations that are amenable to treatment with tyrosine kinase inhibitors. We sought to define the prevalence and genomic landscape of Ph-like ALL in adults and assess response to conventional chemotherapy. Patients and Methods The frequency of Ph-like ALL was assessed by gene expression profiling of 798 patients with B-cell ALL age 21 to 86 years. Event-free survival and overall survival were determined for Ph-like ALL versus non-Ph-like ALL patients. Detailed genomic analysis was performed on 180 of 194 patients with Ph-like ALL. Results Patients with Ph-like ALL accounted for more than 20% of adults with ALL, including 27.9% of young adults (age 21 to 39 years), 20.4% of adults (age 40 to 59 years), and 24.0% of older adults (age 60 to 86 years). Overall, patients with Ph-like ALL had an inferior 5-year event-free survival compared with patients with non-Ph-like ALL (22.5% [95% CI, 14.9% to 29.3%; n = 155] v 49.3% [95% CI, 42.8% to 56.2%; n = 247], respectively; P < .001). We identified kinase-activating alterations in 88% of patients with Ph-like ALL, including CRLF2 rearrangements (51%), ABL class fusions (9.8%), JAK2 or EPOR rearrangements (12.4%), other JAK-STAT sequence mutations (7.2%), other kinase alterations (4.1%), and Ras pathway mutations (3.6%). Eleven new kinase rearrangements were identified, including four involving new kinase or cytokine receptor genes and seven involving new partners for previously identified genes. Conclusion Ph-like ALL is a highly prevalent subtype of ALL in adults and is associated with poor outcome. The diverse range of kinase-activating alterations in Ph-like ALL has important therapeutic implications. Trials comparing the addition of tyrosine kinase inhibitors to conventional therapy are required to evaluate the clinical utility of these agents in the treatment of Ph-like ALL.
AB - Purpose Philadelphia chromosome (Ph) -like acute lymphoblastic leukemia (ALL) is a high-risk subtype of childhood ALL characterized by kinase-activating alterations that are amenable to treatment with tyrosine kinase inhibitors. We sought to define the prevalence and genomic landscape of Ph-like ALL in adults and assess response to conventional chemotherapy. Patients and Methods The frequency of Ph-like ALL was assessed by gene expression profiling of 798 patients with B-cell ALL age 21 to 86 years. Event-free survival and overall survival were determined for Ph-like ALL versus non-Ph-like ALL patients. Detailed genomic analysis was performed on 180 of 194 patients with Ph-like ALL. Results Patients with Ph-like ALL accounted for more than 20% of adults with ALL, including 27.9% of young adults (age 21 to 39 years), 20.4% of adults (age 40 to 59 years), and 24.0% of older adults (age 60 to 86 years). Overall, patients with Ph-like ALL had an inferior 5-year event-free survival compared with patients with non-Ph-like ALL (22.5% [95% CI, 14.9% to 29.3%; n = 155] v 49.3% [95% CI, 42.8% to 56.2%; n = 247], respectively; P < .001). We identified kinase-activating alterations in 88% of patients with Ph-like ALL, including CRLF2 rearrangements (51%), ABL class fusions (9.8%), JAK2 or EPOR rearrangements (12.4%), other JAK-STAT sequence mutations (7.2%), other kinase alterations (4.1%), and Ras pathway mutations (3.6%). Eleven new kinase rearrangements were identified, including four involving new kinase or cytokine receptor genes and seven involving new partners for previously identified genes. Conclusion Ph-like ALL is a highly prevalent subtype of ALL in adults and is associated with poor outcome. The diverse range of kinase-activating alterations in Ph-like ALL has important therapeutic implications. Trials comparing the addition of tyrosine kinase inhibitors to conventional therapy are required to evaluate the clinical utility of these agents in the treatment of Ph-like ALL.
UR - http://www.scopus.com/inward/record.url?scp=85016717027&partnerID=8YFLogxK
U2 - 10.1200/JCO.2016.69.0073
DO - 10.1200/JCO.2016.69.0073
M3 - Article
C2 - 27870571
AN - SCOPUS:85016717027
SN - 0732-183X
VL - 35
SP - 394
EP - 401
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 4
ER -