Clinical efficacy of ruxolitinib and chemotherapy in a child with Philadelphia chromosome-like acute lymphoblastic leukemia with GOLGA5-JAK2 fusion and induction failure.
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ABSTRACT:
SUBMITTER: Ding YY
PROVIDER: S-EPMC6119161 | biostudies-literature | 2018 Sep
REPOSITORIES: biostudies-literature
Publications
Clinical efficacy of ruxolitinib and chemotherapy in a child with Philadelphia chromosome-like acute lymphoblastic leukemia with <i>GOLGA5-JAK2</i> fusion and induction failure.
Ding Yang Y YY Stern Julie W JW Jubelirer Tracey F TF Wertheim Gerald B GB Lin Fumin F Chang Fengqi F Gu Zhaohui Z Mullighan Charles G CG Li Yong Y Harvey Richard C RC Chen I-Ming IM Willman Cheryl L CL Hunger Stephen P SP Li Marilyn M MM Tasian Sarah K SK
Haematologica 20180517 9
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Project description:Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a recently described B-cell precursor ALL with a gene expression profile and a high frequency of IKZF1 gene alteration similar to that of Ph-positive ALL. Its prevalence is approximately 12% in children, 21% in adolescents (16-20 years of age), and 20% to 24% in adults older than 40 years, with a peak (27%) in young adults 21 to 39 years old. It occurs more often in male individuals and patients with Down syndrome. Ph-like ALL is overrepresented in those with Hispanic ethnicity and is associated with inherited genetic variants in GATA3 (rs3824662). It is a clinically and biologically heterogeneous subtype of B-ALL. Although most patients with Ph-like ALL have positive minimal residual disease after remission induction and poor event-free survival, approximately 40% of pediatric patients responded well to chemotherapy and can be cured with relatively low intensity of treatment. The treatment outcome correlated negatively with increasing age at presentation. Ph-like ALL is characterized by a wide range of genetic alterations that dysregulate several cytokine receptor and kinase signaling pathways, including CRLF2 rearrangement in half of the cases and translocation of nonreceptor tyrosine kinases (predominantly ABL-class and Janus kinases). Patients with ABL-class fusions respond clinically to ABL1 tyrosine kinase inhibitors, whereas mutations activating the JAK-STAT pathway are amendable to treatment with JAK inhibitors in vitro or in preclinical models. Prospective studies are needed to determine if incorporation of tyrosine kinase inhibitor targeting kinase alterations into intensive chemotherapy regimens will improve outcome of patients with Ph-like ALL.
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