Abstract
Pediatric acute lymphoblastic leukemia (ALL) with t(9;22)(q34;q11.2) is a very rare malignancy in children. Approximately 3–5% of pediatric ALL patients present with the Philadelphia chromosome. Previously, children with Ph+ had a poor prognosis, and were considered for allogeneic stem cell transplantation (allo-HSCT) in their first remission (CR1). Over the last few years, the treatment of childhood ALL has significantly improved due to standardized research protocols. Hematopoietic stem cell transplantation (HSCT) has been the gold standard therapy in ALL Ph+ patients, but recently first-generation tyrosine kinase inhibitor (TKI)-imatinib became a major milestone in increasing overall survival. Genomic analyses give the opportunity for the investigation of new fusions or mutations, which can be used to establish effective targeted therapies. Alterations of the IKZF1 gene are present in a large proportion of pediatric and adult ALL Ph+ cases. IKZF1 deletions are present in ~15% of patients without BCR-ABL1 rearrangements. In BCR-ABL1-negative cases, IKZF1 deletions have been shown to have an independent prognostic impact, carrying a three-fold increased risk of treatment failure. The prognostic significance of IKZF1 gene aberrations in pediatric ALL Ph+ is still under investigation. More research should focus on targeted therapies and immunotherapy, which is not associated with serious toxicity in the same way as classic chemotherapy, and on the improvement of patient outcomes. In this review, we provide a molecular analysis of childhood ALL with t(9;22)(q34;q11.2), including the Ph-like subtype, and of treatment strategies.
Highlights
Acute lymphoblastic leukemia (ALL) is the most common malignancy diagnosed in children according to American Cancer Society data, accounting for 26% of all cancers in children aged 1–14 and 8% in teenagers aged 15–19 in the USA [1]
In the few years, the genomic landscape of acute lymphoblastic leukemia (ALL) Philadelphia chromosome (Ph)+ will be completely described, which will provide the basis for further research into treatments
Molecular research allowed us to distinguish a new group of ALL, Ph-like ALL, which is characterized by broad-spectrum genetic alterations, but does not have an exact BCRL/ABL1 fusion
Summary
Acute lymphoblastic leukemia (ALL) is the most common malignancy diagnosed in children according to American Cancer Society data, accounting for 26% of all cancers in children aged 1–14 and 8% in teenagers aged 15–19 in the USA [1]. The major difference to the previous study was that in EsPhALL2010 all patients were continuously given imatinib, along with chemotherapy, from Day 15 of induction to the end of the treatment. Current clinical trials suggest that chemotherapy plus imatinib could improve the treatment results for ALL Ph+ patients. Therapeutic failure in ALL Ph+ could be the result of resistance to TKI-based therapies, caused by point mutations in the BCR-ABL1 kinase domain. Some studies have indicated that the second-generation tyrosine kinase inhibitors, including dasatinib and nilotinib, should be considered in ALL Ph+ treatment, because they appear to be more effective in the suppression of BCR-ABL1 kinase activity [20,21,22]. The 4-year OS rate among all patients was 78.1 ± 6.5% [28]
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