We found that blast phase of PV was characterized by overt myelodysplasia (n = 51, 88%); moderate to severe myelofibrosis (33 of 45, 73%); an abnormal karyotype (n = 51, 88%) that was often complex karyotype (n = 42, 72%); and gene mutations involving TP53 (55%), TET2 (27%), and DNMT3A (25%).
We report the occurrence of choroid plexus carcinoma, Spitzoid melanoma, and myelodysplasia in a child who was found to carry a germline mutation for TP53.
Recent studies are shedding light on the molecular basis of myelodysplasia and how mutations and epimutations can induce and promote this neoplastic process through aberrant transcription factor function (RUNX1, ETV6, TP53), kinase signalling (FLT3, NRAS, KIT, CBL) and epigenetic deregulation (TET2, IDH1/2, DNMT3A, EZH2, ASXL1, SF3B1, U2AF1, SRSF2, ZRSR2).
Whereas loss of p53 function promotes leukemia and lymphoma development in humans and mice, increased p53 activity inhibits hematopoietic stem cell function and results in myelodysplasia.
Mutations with loss of heterozygosity of p53 are common in therapy-related myelodysplasia and acute myeloid leukemia after exposure to alkylating agents and significantly associated with deletion or loss of 5q, a complex karyotype, and a poor prognosis.
Consequently, this study revealed a possible relationship of RER+ phenotype accompanying an hMSH2 alteration to the development of therapy-related AML/MDS in association with TP53 mutations and specific chromosomal losses, and suggests that some patients may be predisposed to myelodysplasia after chemotherapy for their primary tumor.
This study suggests that germline p53 mutations may predispose some children to therapy-related leukemia and myelodysplasia, but that p53 mutations otherwise are infrequent in this setting.
Elevated levels of p53 protein in the neutrophils and monocytes of a patient with chronic idiopathic thrombocytopenic purpura or possible early myelodysplasia?