Acute lymphoblastic leukemia (ALL) is an aggressive neoplasm of B- or T-lymphoid progenitors and is the commonest childhood tumor. ALL comprises multiple subtypes characterized by distinct genetic alterations, with stereotyped patterns of aneuploidy present in many cases. Although alterations of TP53 are common in many tumors, they are infrequent in ALL, with the exception of two ALL subtypes associated with poor outcome: relapsed disease and ALL with hypodiploidy. TP53 alterations are present in almost all cases of ALL with low hypodiploidy and are associated with alterations of the lymphoid transcription factor IKZF2 and the tumor-suppressor gene loci CDKN2A and CDKN2B. Remarkably, more than half of TP53 mutations in low-hypodiploid ALL in children are present in nontumor cells, indicating that low-hypodiploid ALL is a manifestation of Li-Fraumeni syndrome. These findings have profound implications for our understanding of the genetic pathogenesis of hypodiploid ALL, suggesting that alteration of TP53 function may promote the distinctive aneuploidy characteristic of hypodiploid ALL. Moreover, the identification of hypodiploidy mandates offering testing for TP53 mutational status to patients and their relatives, with appropria...Continue Reading
Near-haploid common acute lymphoblastic leukaemia of childhood with a second hyperdiploid line: a DNA ploidy and fluorescence in-situ hybridization study
A bipartite nuclear localization signal is required for p53 nuclear import regulated by a carboxyl-terminal domain.
Prognostic value of tumoral ploidy in a series of spanish patients with acute lymphoblastic leukemia
Reassessment of the prognostic significance of hypodiploidy in pediatric patients with acute lymphoblastic leukemia
Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database
Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia.
Cytogenetic and molecular genetic characterization of the 'high hyperdiploid' B-cell precursor acute lymphoblastic leukaemia cell line MHH-CALL-2 reveals a near-haploid origin
Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: a prospective observational study
Key pathways are frequently mutated in high-risk childhood acute lymphoblastic leukemia: a report from the Children's Oncology Group.
Mutations and deletions of the TP53 gene predict nonresponse to treatment and poor outcome in first relapse of childhood acute lymphoblastic leukemia
Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations.
Loss of chromosomes is the primary event in near-haploid and low-hypodiploid acute lymphoblastic leukemia
Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia.
Identification of TP53 as an acute lymphocytic leukemia susceptibility gene through exome sequencing
TP53 mutations are frequent in adult acute lymphoblastic leukemia cases negative for recurrent fusion genes and correlate with poor response to induction therapy
Genes commonly deleted in childhood B-cell precursor acute lymphoblastic leukemia: association with cytogenetics and clinical features
Acute lymphoblastic leukemia with low hypodiploid/near triploid karyotype is a specific clinical entity and exhibits a very high TP53 mutation frequency of 93%
Pediatric ALL relapses after allo-SCT show high individuality, clonal dynamics, selective pressure, and druggable targets
Targeting p53-MDM2 Interaction Using Small Molecule Inhibitors and the Challenges Needed to be Addressed
Unmanipulated haploidentical peripheral blood stem cell transplantation for patients with Philadelphia-negative acute lymphoblastic leukaemia in first complete remission.
Aggressive morphologic variants of mantle cell lymphoma characterized with high genomic instability showing frequent chromothripsis, CDKN2A/B loss, and TP53 mutations: A multi-institutional study.
New Challenges in Targeting Signaling Pathways in Acute Lymphoblastic Leukemia by NGS Approaches: An Update
Therapy-related B-cell acute lymphoblastic leukemia in adults has unique genetic profile with frequent loss of TP53 and inferior outcome.
Single nucleotide polymorphism array-based signature of low hypodiploidy in acute lymphoblastic leukemia.
The Emerging Role of Hematopathologists and Molecular Pathologists in Detection, Monitoring, and Management of Myeloid Neoplasms with Germline Predisposition.
Mutant p53-reactivating compound APR-246 synergizes with asparaginase in inducing growth suppression in acute lymphoblastic leukemia cells.
B-cell acute lymphoblastic leukaemia: recent discoveries in molecular pathology, their prognostic significance, and a review of the current classification.
Blood And Marrow Transplantation
The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.