TY - JOUR
T1 - Rearrangements involving 11q23.3/KMT2A in adult AML
T2 - mutational landscape and prognostic implications - a HARMONY study
AU - Hernandez-Sanchez, Alberto
AU - Gonzalez, Teresa
AU - Sobas, Marta
AU - Straeng, Eric
AU - Castellani, Gastone
AU - Abaigar, Maria
AU - Valk, Peter J. M.
AU - Ramiro, Angela Villaverde
AU - Benner, Axel
AU - Metzeler, Klaus H.
AU - Azibeiro, Raul
AU - Tettero, Jesse M.
AU - Martinez-Lopez, Joaquin
AU - Pratcorona, Marta
AU - Elicegui, Javier Martinez
AU - Mills, Ken I.
AU - Thiede, Christian
AU - Sanz, Guillermo
AU - Doehner, Konstanze
AU - Heuser, Michael
AU - Haferlach, Torsten
AU - Turki, Amin T.
AU - Reinhardt, Dirk
AU - Schulze-Rath, Renate
AU - Barbus, Martje
AU - Hernandez-Rivas, Jesus Maria
AU - Huntly, Brian
AU - Ossenkoppele, Gert
AU - Doehner, Hartmut
AU - Bullinger, Lars
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/7
Y1 - 2024/7
N2 - Balanced rearrangements involving the KMT2A gene (KMT2Ar) are recurrent genetic abnormalities in acute myeloid leukemia (AML), but there is lack of consensus regarding the prognostic impact of different fusion partners. Moreover, prognostic implications of gene mutations co-occurring with KMT2Ar are not established. From the HARMONY AML database 205 KMT2Ar adult patients were selected, 185 of whom had mutational information by a panel-based next-generation sequencing analysis. Overall survival (OS) was similar across the different translocations, including t(9;11)(p21.3;q23.3)/KMT2A::MLLT3 (p = 0.756). However, independent prognostic factors for OS in intensively treated patients were age >60 years (HR 2.1, p = 0.001), secondary AML (HR 2.2, p = 0.043), DNMT3A-mut (HR 2.1, p = 0.047) and KRAS-mut (HR 2.0, p = 0.005). In the subset of patients with de novo AML < 60 years, KRAS and TP53 were the prognostically most relevant mutated genes, as patients with a mutation of any of those two genes had a lower complete remission rate (50% vs 86%, p < 0.001) and inferior OS (median 7 vs 30 months, p < 0.001). Allogeneic hematopoietic stem cell transplantation in first complete remission was able to improve OS (p = 0.003). Our study highlights the importance of the mutational patterns in adult KMT2Ar AML and provides new insights into more accurate prognostic stratification of these patients. (Figure presented.).
AB - Balanced rearrangements involving the KMT2A gene (KMT2Ar) are recurrent genetic abnormalities in acute myeloid leukemia (AML), but there is lack of consensus regarding the prognostic impact of different fusion partners. Moreover, prognostic implications of gene mutations co-occurring with KMT2Ar are not established. From the HARMONY AML database 205 KMT2Ar adult patients were selected, 185 of whom had mutational information by a panel-based next-generation sequencing analysis. Overall survival (OS) was similar across the different translocations, including t(9;11)(p21.3;q23.3)/KMT2A::MLLT3 (p = 0.756). However, independent prognostic factors for OS in intensively treated patients were age >60 years (HR 2.1, p = 0.001), secondary AML (HR 2.2, p = 0.043), DNMT3A-mut (HR 2.1, p = 0.047) and KRAS-mut (HR 2.0, p = 0.005). In the subset of patients with de novo AML < 60 years, KRAS and TP53 were the prognostically most relevant mutated genes, as patients with a mutation of any of those two genes had a lower complete remission rate (50% vs 86%, p < 0.001) and inferior OS (median 7 vs 30 months, p < 0.001). Allogeneic hematopoietic stem cell transplantation in first complete remission was able to improve OS (p = 0.003). Our study highlights the importance of the mutational patterns in adult KMT2Ar AML and provides new insights into more accurate prognostic stratification of these patients. (Figure presented.).
UR - http://www.scopus.com/inward/record.url?scp=85197558878&partnerID=8YFLogxK
U2 - 10.1038/s41375-024-02333-4
DO - 10.1038/s41375-024-02333-4
M3 - Article
C2 - 38965370
SN - 0887-6924
VL - 38
SP - 1929
EP - 1937
JO - Leukemia
JF - Leukemia
IS - 9
ER -
