TP53 mutation in children with therapy-related myelodysplastic syndrome/acute myeloid leukemia after rhabdomyosarcoma treatment
Abstract
After successful treatment of childhood malignancy, development of second malignancy (SM) is the most
devastating and potentially life-threatening sequelae of it. In the past 12 years there have been no cases
of therapy-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) among 80 children
treated for soft tissue sarcomas (STS) in the Department of Paediatric Oncology, Haematology, and Bone
Marrow Transplantation. Given the rarity of recognition of t-MDS/AML in children after treatment of
cancers, it was decided to analyse in detail the therapy and cytogenetic and molecular results in two boys
aged 9 and 10 years old, diagnosed with t-MDS/AML secondary to rhabdomyosarcoma. In both of them
TP53 mutation was found.
Palliat Med Pract 2020; 14, 1: 58–62
Keywords: acute myeloid leukaemiachildrenmyelodysplastic syndromerhabdomyosarcomaTP53 mutation
References
- Hijiya N, Ness KK, Ribeiro RC, et al. Acute leukemia as a secondary malignancy in children and adolescents: current findings and issues. Cancer. 2009; 115(1): 23–35.
- Pedersen-Bjergaard J, Andersen MK, Christiansen DH. Therapy-related acute myeloid leukemia and myelodysplasia after high-dose chemotherapy and autologous stem cell transplantation. Blood. 2000; 95(11): 3273–3279.
- Pedersen-Bjergaard J, Andersen MK, Andersen MT, et al. Genetic pathways in therapy-related myelodysplasia and acute myeloid leukemia. Blood. 2002; 99(6): 1909–1912.
- Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016; 127(20): 2391–2405.
- Hasle H. Myelodysplastic and myeloproliferative disorders of childhood. Hematology Am Soc Hematol Educ Program. 2016; 2016(1): 598–604.
- Hong M, He G. The 2016 Revision to the World Health Organization Classification of Myelodysplastic Syndromes. J Transl Int Med. 2017; 5(3): 139–143.
- Ogasawara T, Yasuyama M, Kawauchi K. Therapy-related myelodysplastic syndrome with monosomy 5 after successful treatment of acute myeloid leukemia (M2). Am J Hematol. 2005; 79(2): 136–141.
- Navid F, Billups C. Second Cancers in patients with ESFT. Eur J Cancer. 2008; 44: 983–991.
- Bhatia S, Krailo MD, Chen Z, et al. Therapy-related myelodysplasia and acute myeloid leukemia after Ewing sarcoma and primitive neuroectodermal tumor of bone: A report from the Children's Oncology Group. Blood. 2007; 109(1): 46–51.
- Andersen MK, Christiansen DH, Pedersen-Bjergaard J. Centromeric breakage and highly rearranged chromosome derivatives associated with mutations of TP53 are common in therapy-related MDS and AML after therapy with alkylating agents: an M-FISH study. Genes Chromosomes Cancer. 2005; 42(4): 358–371.
- Sans-Sabrafen J, Buxó-Costa J, Woessner S, et al. Myelodysplastic syndromes and malignant solid tumors: analysis of 21 cases. Am J Hematol. 1992; 41(1): 1–4.
- el Rouby S, Thomas A, Costin D, et al. p53 gene mutation in B-cell chronic lymphocytic leukemia is associated with drug resistance and is independent of MDR1/MDR3 gene expression. Blood. 1993; 82(11): 3452–3459.
- Andersen MK, Christiansen DH, Pedersen-Bjergaard J. Centromeric breakage and highly rearranged chromosome derivatives associated with mutations of TP53 are common in therapy-related MDS and AML after therapy with alkylating agents: an M-FISH study. Genes Chromosomes Cancer. 2005; 42(4): 358–371.
- Nadji M, Meng L, Lin L, et al. Detection of p53 gene abnormality by sequence analysis of archival paraffin tissue. A comparison with fresh-frozen specimens. Diagn Mol Pathol. 1996; 5(4): 279–283.
- Meng L, Lin L, Zhang H, et al. Multiple mutations of the p53 gene in human mammary carcinoma. Mutat Res. 1999; 435(3): 263–269.
- Belickova M, Vesela J, Jonasova A, et al. TP53 mutation variant allele frequency is a potential predictor for clinical outcome of patients with lower-risk myelodysplastic syndromes. Oncotarget. 2016; 7(24): 36266–36279.
- Ruijs MWG, Verhoef S, Rookus MA, et al. TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes. J Med Genet. 2010; 47(6): 421–428.
- Seki M, Nishimura R, Yoshida K, et al. Integrated genetic and epigenetic analysis defines novel molecular subgroups in rhabdomyosarcoma. Nat Commun. 2015; 6: 7557.
- Hettmer S, Archer NM, Somers GR, et al. Anaplastic rhabdomyosarcoma in TP53 germline mutation carriers. Cancer. 2014; 120(7): 1068–1075.
- Takahashi Y, Oda Y, Kawaguchi KI, et al. Altered expression and molecular abnormalities of cell-cycle-regulatory proteins in rhabdomyosarcoma. Mod Pathol. 2004; 17(6): 660–669.
- Kobos R, Steinherz PG, Kernan NA, et al. Allogeneic hematopoietic stem cell transplantation for pediatric patients with treatment-related myelodysplastic syndrome or acute myelogenous leukemia. Biol Blood Marrow Transplant. 2012; 18(3): 473–480.
- Niemeyer CM, Kratz CP, Hasle H. Pediatric myelodysplastic syndromes. Curr Treat Options Oncol. 2005; 6(3): 209–214.
- Strahm B, Locatelli F, Bader P, et al. Reduced intensity conditioning in unrelated donor transplantation for refractory cytopenia in childhood. Bone Marrow Transplant. 2007; 40(4): 329–333.
- Welch JS, Petti AA, Miller CA, et al. TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes. N Engl J Med. 2016; 375(21): 2023–2036.
- Cseh AM, Niemeyer CM, Yoshimi A, et al. Therapy with low-dose azacitidine for MDS in children and young adults: a retrospective analysis of the EWOG-MDS study group. Br J Haematol. 2016; 172(6): 930–936.
- Singhal D, Wee LiY, Kutyna MM, et al. The mutational burden of therapy-related myeloid neoplasms is similar to primary myelodysplastic syndrome but has a distinctive distribution. Leukemia. 2019; 33(12): 2842–2853.