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Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] - General Information About Childhood Acute Lymphoblastic Leukemia (ALL)

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Inherited genetic polymorphisms

Genome-wide association studies show that some germline (inherited) genetic polymorphisms are associated with the development of childhood ALL.[29] For example, the risk alleles of ARID5B are strongly associated with the development of hyperdiploid B-precursor ALL. ARID5B is a gene that encodes a transcriptional factor important in embryonic development, cell type–specific gene expression, and cell growth regulation.[30,31]

Prenatal origin of childhood ALL

Development of ALL is in most cases a multi-step process, with more than one genomic alteration required for frank leukemia to develop. In at least some cases of childhood ALL, the initial genomic alteration appears to occur in utero. Evidence in support of this comes from the observation that the immunoglobulin or T-cell receptor antigen rearrangements that are unique to each patient's leukemia cells can be detected in blood samples obtained at birth.[32,33] Similarly, in ALL characterized by specific chromosomal abnormalities, some patients appear to have blood cells carrying at least one leukemic genomic abnormality at the time of birth, with additional cooperative genomic changes acquired postnatally.[32,33,34] Genomic studies of identical twins with concordant leukemia further support the prenatal origin of some leukemias.[32,35]

There is also evidence that some children who never develop ALL are born with very rare blood cells carrying a genomic alteration associated with ALL. For example, in one study, 1% of neonatal blood spots (Guthrie cards) tested positive for the ETV6-RUNX1 translocation, far exceeding the number of cases of ETV6-RUNX1 ALL in children.[36] Other reports confirm [37] or do not confirm [38] this finding. Nonetheless, if confirmed, it would support the hypothesis that additional postnatal genomic changes are needed for the development of this type of ALL and that in most cases in which a leukemia-associated alteration is present at birth, the additional leukemogenic genomic changes do not occur and no leukemia develops.

Clinical Presentation

The typical and atypical symptoms and clinical findings of childhood ALL have been published.[39,40,41]

Diagnosis

The diagnostic evaluation needed to definitively diagnose childhood ALL has been published.[39,40,41,42]

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