Complex Karyotype and TP53 Alterations in AML and MDS

Background/Objectives: A complex karyotype (CK) in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDSs) is defined as the presence of three or more unrelated chromosomal abnormalities in the absence of defining core-binding factor translocations. Losses/Deletions on chromosomes 5, 7 and 17 are frequently observed. It is heavily associated with TP53 mutations, with 70–80% of CK cases in MDS/AML harboring TP53 mutations. Methods: An extensive literature search of the studies carried out in the last two decades has shown a consistent development of experimental and clinical studies aiming to characterize the biological properties and clinical features of AML and MDS bearing CK and TP53 mutations. Results: These studies have greatly contributed to identifying as separate entities AML and MDS bearing CK and or TP53 alterations. Particularly, the improvement in the methods of detection of chromosome aberrations has contributed to defining the specific nature of the various chromosome abnormalities and to deciphering the mechanisms of catastrophic events leading to gene rearrangements. Two types of CK were identified in AML and MDS, one more frequently associated with TP53 mutations (with poor prognosis) and another less frequently without TP53 mutations (with relatively better prognosis). Conclusions: The treatment of AML and MDS with CK and/or TP53 mutations alterations remains extremely challenging, and the prognosis of these patients is dismal. The main aim of the various induction treatments explored in these patients is to bridge patients to allo-HSCT, the only therapeutic approach able to improve the survival of at least a part of these patients.