Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia: Progress in a New Cancer Subtype
CLINICAL ADVANCES IN HEMATOLOGY & ONCOLOGY
Authors: Wells, Julia; Jain, Nitin; Konopleva, Marina
Abstract
Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) is a newly described, high-risk subtype of B-cell ALL. It is characterized by a gene expression profile similar to that of Ph-positive ALL; however, the BCR-ABL1 fusion is not present. The World Health Organization classification of myeloid neoplasms and acute leukemia recently was updated to include the Ph-like or BCR-ABL1-like ALL subtype of B-cell ALL as a provisional entity. Unlike Ph-positive ALL, which is characterized by the pathognomonic BCR-ABL1 fusion, Ph-like ALL is characterized by a multitude of different genetic rearrangements and mutations. In this review, we outline the age-related and geographic incidence of Ph-like ALL, the association with worse clinical outcomes, and early evidence for the use of ruxolitinib (a Janus kinase 2 inhibitor) and dasatinib (a tyrosine kinase inhibitor targeting ABL1).
Biology of Childhood Acute Lymphoblastic Leukemia
JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
Authors: Lo Nigro, Luca
Abstract
Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood, accounting for almost 30% of pediatric cancers. Despite the high rate of cure, ALL is one of the leading causes of death in children with tumor. For this reason, there is a keen interest in identifying genetic and biological features that influence the pathogenesis of ALL and the risk of treatment failure. The application of standard diagnostic technologies such as a conventional karyotype and polymerase chain reaction methodologies, together with gene expression profiling and genome-wide analyses, allows us to genetically characterize almost 100% of children with ALL. This review provides basic information about well-established genetic alterations associated with specific clinical subtypes and new molecular lesions with potential prognostic impact. New insights are reported on the natural history of ALL. Genetic aberrations in childhood ALL are considered both markers of disease and potential targets of treatment. Here, each biological subtype under the genetic point of view has been dissected, including genes involved in the development of lymphocytes and considerations on ALL in infancy. It is also crucial to discuss the issue of relapse. Finally, as future treatment will be individualized on the basis of biological features, the pediatric hemato-oncologists need to be ready and prepared to tailor the "right treatment" to the "right children" with ALL.