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Review
. 2023 Mar 8;11(3):821.
doi: 10.3390/biomedicines11030821.

Updates in KMT2A Gene Rearrangement in Pediatric Acute Lymphoblastic Leukemia

Mateusz Górecki  1 , Ilona Kozioł  2 , Agnieszka Kopystecka  2 , Julia Budzyńska  2 , Joanna Zawitkowska  3 , Monika Lejman  4
Affiliations
Review

Updates in KMT2A Gene Rearrangement in Pediatric Acute Lymphoblastic Leukemia

Mateusz Górecki et al. Biomedicines. .

Abstract

The KMT2A (formerly MLL) encodes the histone lysine-specific N-methyltransferase 2A and is mapped on chromosome 11q23. KMT2A is a frequent target for recurrent translocations in acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or mixed lineage (biphenotypic) leukemia (MLL). Over 90 KMT2A fusion partners have been identified until now, including the most recurring ones-AFF1, MLLT1, and MLLT3-which encode proteins regulating epigenetic mechanisms. The presence of distinct KMT2A rearrangements is an independent dismal prognostic factor, while very few KMT2A rearrangements display either a good or intermediate outcome. KMT2A-rearranged (KMT2A-r) ALL affects more than 70% of new ALL diagnoses in infants (<1 year of age), 5-6% of pediatric cases, and 15% of adult cases. KMT2A-rearranged (KMT2A-r) ALL is characterized by hyperleukocytosis, a relatively high incidence of central nervous system (CNS) involvement, an aggressive course with early relapse, and early relapses resulting in poor prognosis. The exact pathways of fusions and the effects on the final phenotypic activity of the disease are still subjects of much research. Future trials could consider the inclusion of targeted immunotherapeutic agents and prioritize the identification of prognostic factors, allowing for the less intensive treatment of some infants with KMT2A ALL. The aim of this review is to summarize our knowledge and present current insight into the mechanisms of KMT2A-r ALL, portray their characteristics, discuss the clinical outcome along with risk stratification, and present novel therapeutic strategies.

Keywords: KMT2A-r; acute lymphoblastic leukemia; infant.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Relationship between KMT2A fusion partner and median survival rate in infant KMT2A-r ALL.
Figure 2
Figure 2
Relationship between KMT2A fusion partner and median survival rate in pediatric KMT2A-r ALL.
Figure 3
Figure 3
KMT2A-r ALL—potential therapeutic targets discussed in the review. HDAC—histone deacetylase; FLT3—fms-like tyrosine kinase 3; CART T-cell—chimeric antigen receptor T-cell; HSCT—hematopoietic stem cell transplantation.
Figure 4
Figure 4
Mechanism of action of HDAC inhibitors. HATs-histone acetylases, HDACs-histone deacetylases.
See this image and copyright information in PMC

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