We conclude that IKZF1 and TP53 represent relevant prognostic factors that should be considered in future risk assessment of children with relapsed ALL to indicate treatment intensification or intervention.
Treatments with compounds that may reverse the epigenetic abnormalities or activate directly the p53 pathway represent a new therapeutic alternative for patients with ALL.
To understand the role of p53 abnormalities in this clinical setting, it will be important for future studies to analyze cases of relapsed ALL with assays capable of interrogating the functional integrity of the p53 pathway.
We have performed an exhaustive analysis of TP53, p14, p15, and p16 status in a large series of 143 soft tissue sarcomas, rare tumors accounting for around 1% of all adult cancers, with complex genetics.
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.
The indomethacin treatment increased the level of p53 in the leukemic cells, implying that COX inhibition might reduce progression of ALL by attenuating protective paracrine PGE2 signaling from bone marrow stroma to leukemic cells.
MDM-2 expression by flow cytometry and p53 gene status by PCR were determined in peripheral blood or bone marrow of 46 ALL children (at initial diagnosis) and control group.
Summarizing, (1) loss of Rb expression is common in adult ALL; (2) overexpression of p53 may be more frequent in relapsed/refractory than de novo adult ALL; and (3) although Rb or p53 alterations alone are not strong independent predictors of outcome, their concurrent expression may predict a poor response to therapy.
Ninety-one children with untreated acute lymphoblastic leukemia (ALL) were analysed for expression of p53 using immunocytochemistry. p53 expression was found in 80% of the cases by Mab 421.
We report that p53 inactivation in ALL of B cell lineage is restricted to cases carrying a rearrangement of MLL or c-MYC, whereas it is consistently negative in other molecular subgroups.
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.
The expression of p53 was studied in 9 cell lines and 17 de novo acute leukemia (9 acute myeloid leukemia [AML], 8 acute lymphoblastic leukemia [ALL]) patients.
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.