RESUMO
Chromosomal rearrangements of the human KMT2A/MLL gene are associated with de novo as well as therapy-induced infant, pediatric, and adult acute leukemias. Here, we present the data obtained from 3401 acute leukemia patients that have been analyzed between 2003 and 2022. Genomic breakpoints within the KMT2A gene and the involved translocation partner genes (TPGs) and KMT2A-partial tandem duplications (PTDs) were determined. Including the published data from the literature, a total of 107 in-frame KMT2A gene fusions have been identified so far. Further 16 rearrangements were out-of-frame fusions, 18 patients had no partner gene fused to 5'-KMT2A, two patients had a 5'-KMT2A deletion, and one ETV6::RUNX1 patient had an KMT2A insertion at the breakpoint. The seven most frequent TPGs and PTDs account for more than 90% of all recombinations of the KMT2A, 37 occur recurrently and 63 were identified so far only once. This study provides a comprehensive analysis of the KMT2A recombinome in acute leukemia patients. Besides the scientific gain of information, genomic breakpoint sequences of these patients were used to monitor minimal residual disease (MRD). Thus, this work may be directly translated from the bench to the bedside of patients and meet the clinical needs to improve patient survival.
Assuntos
Histona-Lisina N-Metiltransferase , Leucemia Mieloide Aguda , Proteína de Leucina Linfoide-Mieloide , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Leucemia Mieloide Aguda/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Histona-Lisina N-Metiltransferase/genética , Proteína de Leucina Linfoide-Mieloide/genética , Fusão GênicaRESUMO
Acute promyelocytic leukemia (APL) is usually associated with a favorable outcome, but about 10% of patients tend to relapse. The genetic hallmark of APL is a balanced translocation involving chromosomes 15 and 17, and the PML-RARa gene fusion is found in more than 90% of these cases. Other chromosomal abnormalities are commonly found in APL, but their clinical significance has yet to be determined. Here we report a case of childhood APL that was studied by conventional cytogenetics along with molecular cytogenetic techniques. The patient showed a complex karyotype with an unusual cytogenetic rearrangement originating from two different abnormalities in a single chromosome 6. Our case is an exceptional example of a cryptic cytogenetic anomaly in APL and underscores the importance of detailed genetic characterization.
