Analysis of fresh human tumors have indicated that patients with B type lymphoproliferative diseases and the majority of patients with acute lymphoblastic leukemia (ALL) express elevated levels of p53 production.
We selected a group of 16 patients with acute lymphoblastic leukemia (ALL) and Burkitt's lymphoma (BL) in order to investigate the presence of p53 mutations.
This study applied two data mining approaches to explore potential interactions among P53 and xenobiotic metabolizing genes in 230 AL patients [131 acute myeloid leukemia (AML) and 99 acute lymphoblastic leukemia (ALL)] and 199 controls.
The other nonhereditary p53 mutation was a transition at codon 248 (CGG to CAG, arginine to glutamine) found in the lymphoblasts of a patient with a preleukemic syndrome and acute lymphoblastic leukemia (ALL) whose brother is a long-term survivor of ALL.
Marked overexpression was found in two cases of T-cell prolymphocytic leukemias and in four B-cell lineage acute lymphoblastic leukemia including one case with the t(8;14) and another case with a p53 mutation.
Low-level DHFR gene amplification may be an important cause of MTX resistance in ALL and strengthens the concept that mutations in the p53 gene may lead to gene amplification as a consequence of defective cell cycle control.
Inactivation of the p53 pathway may, therefore, be important in children with ALL who fail to respond to treatment and may be useful for the early identification of children requiring alternative therapies.
Mutations were detected in samples from two patients with ALL at relapse; these were not detected in samples at initial diagnosis from the same patients, suggesting that p53 mutations may be associated with progression to a more malignant phenotype.
Cells from acute lymphoblastic leukemia (ALL) and Burkitt's lymphoma cell lines express elevated levels of p53, while all examined human acute myeloid leukemia cell lines synthesize negligible p53 protein.
A total of 288 acute leukemia cases comprising 147 acute lymphocytic leukemia (ALL) and 141 acute myeloid leukemia (AML), as well as 245 controls were recruited for analysis of the TP53 72 polymorphism using PCR-RFLP method.
The mutations of the p53 gene were found in 2 of 20 t(1;19)-ALL cases at diagnosis (10%), all of 4 cases at relapse (100%), and 4 of the 5 cell lines (80%).
A novel 8-bp insertion in codon 281 of p53 in a patient with acute lymphoblastic leukaemia and 2 separate leukaemic clones. Mutations in brief no. 219. Online.
Taken together, the 2 cell lines had features of Ph1-positive ALL: (i) hematopoietic progenitor cells with pre-B-cell phenotype and, (ii) activation of e1-a2 type bcr/abl oncogene without alterations of p53 gene.
The results showed ALL-1 gene rearrangements in 15/22 (68%) cases, p53 gene mutations in 5/22 (26%), and a homozygous deletion of p16 in a single T-ALL case. p53 and p16 alterations were all found in the group of patients with ALL-1 gene rearrangements. p53 mutations were more often associated with a myeloid phenotype (3/5).
There was no clinical, or haematological difference or difference in survival between ras positive and ras negative patients with acute myeloid leukaemia (AML) in adults or children, but ras mutations carried a poorer prognosis in childhood acute lymphocytic leukaemia and an increased risk of leukaemia in MDS. p53 mutations predominated in lymphoid leukaemia and were several fold more frequent in leukaemia in relapse than in the de novo disease, were associated with loss of the normal p53 allele (monosomy 17) in > 50% of cases and carried a poor prognosis in AML, MDS and chronic lymphatic leukaemia and a 3.8-fold increase risk of death in T cell acute lymphocytic leukaemia.
Treatments with compounds that may reverse the epigenetic abnormalities or activate directly the p53 pathway represent a new therapeutic alternative for patients with ALL.