ISSN 1866-8836
Клеточная терапия и трансплантация

AL-08. Heterogeneity of t(10;11) translocation with KMT2A-MLLT10 molecular product in patients with acute myeloid leukemia

Maria V. Stegantseva1, Darya R. Kapuza1, Julia A. Barouskaya1, Maria G. Naumovich1, Veronika А. Astramovich1, Olga V. Aleinikova2

1 Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, v. Borovliany, Minsk District, Republic of Belarus
2 Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia

Contact: Dr. Maria V. Stegantseva, phone: +375 (293) 747-709, e-mail:

doi 10.18620/ctt-1866-8836-2022-11-3-1-132


Detection of KMT2A (MLL) gene translocations in the diagnostics of acute myeloid leukemia (AML) is a mandatory procedure due to the high incidence of these aberrations as well as their impact on the patients stratification by risk groups. t(10;11) is among common chromosomal rearrangements after t(9;11). Its occurrence may be up to 8-9% in the AML structure (D. Steinhilber et al., 2018; T. Ksiazek et al., 2020). The main molecular product of t(10;11) is KMT2A-MLLT10 (MLL-AF10), although other gene products have been described. The chimeric KMT2A-MLLT10 transcript is produced by a variety of mechanisms (Klaus et al., 2003). The diagnostics of this translocation is difficult because of cryptic translocations that are not detected by cytogenetic tests or molecular genetics. This study presents four cases of t(10;11)(p12;q23) with the KMT2A-MLLT10 in the children with acute myeloid leukemia (AML) exhibiting different mechanism of its formation, including one case of cryptic translocation.

Materials and methods

The study includes four children with AML M5, whose median age was 11.3 months. RNA was isolated from the bone marrow (BM) mononuclear cells of the patients. The chimeric transcripts of KMT2A gene (AF4, AF6, AF9, MLLT10, ENL, ELL) were discerned by reverse-transcription PCR (RT-PCR) then being verified by direct Sanger sequencing (A. Andersson et al., 2001). Karyotyping of tumor cells was performed using differential G-staining of preparations from the 24-hour BM cell culture (RPMI-1640 supplemented with 15% fetal calf serum, 1% L-glutamine, 1% antimycotic antibiotic). FISH analysis was performed in interphase nuclei and metaphase plates using a locus-specific two-color DNA probe for the KMT2A gene (11q23) (LSI Dual-Color, Break Apart Rearrangement Probe, Vysis, USA), according to the manufacturer instructions. Analysis and registration of data were carried out in accordance with Guidelines of the International System for Human Cytogenic Nomenclature (ISCN).


103 patients with primary AML were diagnosed at the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology over the period of 2010 to 2021. KMT2A gene rearrangements were detected in 14.6% of patients. KMT2A-MLLT10 was found in 26.6% of KMT2A-positive patients, and in 3.8% of all examined AML patients. Patient #1 (a boy, 4 months) had a complex rearrangement with the visible marker chromosome formed by fusion of chromosomes 10, 11 and 17, with the KMT2A gene involved. The classic fusion product was detected at molecular level, and its sequencing demonstrated a fusion of exon 10 in KMT2A, and exon 9 of MLLT10. The clone of leukemic cells with t(10;11) translocation and inv(11)(q21q23)/KMT2A(+) inversion resulting into the chimeric KMT2A-MLLT10 gene was detected in patient #2 (a girl, 13.2 months). Of note, this rearrangement is the most common. In patient #3 (a girl, 16 years old), standard karyotyping revealed a complex karyotype with unbalanced translocation variant t(10;11), in which only a derivative of chromosome 10 was detected (der(10)t(10;11)(p12;q23q21)amp(5`KMT2A). RT-PCR revealed the KMT2A-MLLT10 product which involved exon 8 of the KMT2A gene and exon 9 of the MLLT10 gene. Cytogenetic analysis did not reveal chromosomal rearrangements associated with acute leukemia in patient #4 (girl, 9 months). At the same time, the KMT2A-MLLT10 chimeric transcript was detected by RT-PCR. Hence, similar molecular products have been detected in all patients, despite sufficient differences at the chromosomal level.


Thorough identification of rearrangements involving KMT2A gene is extremely important for the disease prognosis, and may succeed only by using a combination of standard karyotyping (G-staining) and molecular cytogenetic techniques (FISH and PCR).


Acute myeloid leukemia, diagnostics, KMT2A-MLLT10.

Volume 11, Number 3

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doi 10.18620/ctt-1866-8836-2022-11-3-1-132

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