Abstract
The MLL (mixed-lineage leukemia) gene, located on chromosome 11q23, is involved in chromosomal translocations in a subtype of acute leukemia, which represents approximately 10% of acute lymphoblastic leukemia and 2.8% of acute myeloid leukemia cases. These translocations form fusions with various genes, of which more than 80 partner genes for MLL have been identified. The most recurrent fusion partner in MLL rearrangements (MLL-r) is AF4, mapping at chromosome 4q21, accounting for approximately 36% of MLL-r leukemia and particularly prevalent in MLL-r acute lymphoblastic leukemia (ALL) cases (57%). MLL-r leukemia is associated with a sudden onset, aggressive progression, and notoriously poor prognosis in comparison to non-MLL-r leukemias. Despite modern chemotherapeutic interventions and the use of hematopoietic stem cell transplantations, infants, children, and adults with MLL-r leukemia generally have poor prognosis and response to these treatments. Based on the frequency of patients who relapse, do not achieve complete remission, or have brief event-free survival, there is a clear clinical need for a new effective therapy. In this review, we outline the current therapy options for MLL-r patients and the potential application of CAR-T therapy.
Highlights
Rearrangements of the MLL Gene in LeukemiaRearrangements of the mixed-lineage leukemia ( known as MLL, KMT2A, HRX, or ALL1) gene are found in de novo and therapy-related myeloid and lymphoblastic leukemias, accounting for 9% of adult cases, 3–5% of children [1,2,3,4] and 61–80% of infants in acute lymphoblastic leukemia (ALL) [5,6,7], as well as 5–11% of adult cases, ~15% of children [8,9,10,11] and 33–75% of infant cases in acute myeloid leukemia (AML) [12,13]
The MLL gene, located on chromosome 11q23, is involved in chromosomal translocations in a subtype of acute leukemia, which represents approximately 10% of acute lymphoblastic leukemia and 2.8% of acute myeloid leukemia cases
All patients in high-risk groups are recommended for hematopoietic stem cell transplantation (HSCT) regardless of minimal residual disease (MRD), which may increase the risk of subjecting patients to unnecessary HSCT-related complications
Summary
Rearrangements of the mixed-lineage leukemia ( known as MLL, KMT2A, HRX, or ALL1) gene are found in de novo and therapy-related myeloid and lymphoblastic leukemias, accounting for 9% of adult cases, 3–5% of children [1,2,3,4] and 61–80% of infants in acute lymphoblastic leukemia (ALL) [5,6,7], as well as 5–11% of adult cases, ~15% of children [8,9,10,11] and 33–75% of infant cases in acute myeloid leukemia (AML) [12,13]. MLL rearrangements (MLL-r) are the most prevalent abnormalities in infants and represents one of the most aggressive leukemia subtypes, generally characterized by a rapid onset, hyperleukocytosis, and dismal prognosis [2,14]. The mutational landscape of MLL-leukemias is extraordinarily simple, with a surprisingly low frequency of secondary mutations that may contribute to leukemogenesis [33,34] For this reason, the mechanism by which the t(4;11)(q21;q23) abnormality promotes such an aggressive and clinically challenging phenotype remains unclear [35]. From a biological point of view, gene expression analyses suggest that the development of MLL-driven leukemia in infants is distinct from older children, which could explain the marked, age-dependent differences observed in clinical outcomes [45]. The same rearrangement is shown in (C), obtained by G-banding
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
