Translocation (10;11)(p12;q23) in childhood acute myeloid leukemia: incidence and complex mechanism

Acute leukemias harboring KMT2A/MLLT10 fusion: a 10‐year experience from a single genomics laboratory

“…Furthermore, of the 8 patients who appeared to harbor a reciprocal 10;11 translocation by conventional chromosome analysis, only 1 demonstrated 2 fusion signals by the KMT2A/MLLT10 D‐FISH assay. Deviating from the traditional interpretation of D‐FISH signal patterns, the presence of 2 fusion signals in the KMT2A/MLLT10 D‐FISH assay would not be expected to predict a balanced rearrangement considering the complex rearrangements necessary to create an in‐frame KMT2A/MLLT10 fusion . For example, conventional chromosome and metaphase FISH studies for patient 59 (illustrated in Peterson et al) demonstrated 2 KMT2A/MLLT10 fusion signals located on a marker chromosome.…”

“…To date, the full characterization of KMT2A/MLLT10 gene fusions has heavily relied upon a combination of conventional chromosome, FISH, and reverse transcriptase‐polymerase chain reaction studies . To further characterize 2 cryptic KMT2A/MLLT10 fusions with “normal” chromosomes studies (patients 18 and 48), we performed MPseq, a next‐generation sequencing (NGS)‐based assay that resolves chromosomal rearrangements with significantly higher resolution and precision compared to traditional cytogenetic methodoliges .…”

“…As of 2017, 135 different KMT2A gene fusion partners have been described; however, only 9 partners account for greater than 90% of all KMT2A gene fusions . Observed in approximately 10% of acute leukemias harboring KMT2A rearrangements, MLLT10 (10p12.31) (previously AF10 ) is the fourth most common gene fusion partner and is predominantly observed in pediatric acute myeloid leukemia (AML), although it has been reported in congenital and infant leukemia, therapy‐related AML, B‐ and T‐lymphoblastic leukemia/lymphoma (ALL/LBL), and mixed‐phenotype acute leukemia (MPAL) . Interestingly, a reciprocal 10;11 translocation is insufficient to create an in‐frame KMT2A/MLLT10 fusion as the 3′ segment of KMT2A is oriented to the telomere while the 3′ segment of MLLT10 is oriented to the centromere .…”

“…Interestingly, a reciprocal 10;11 translocation is insufficient to create an in‐frame KMT2A/MLLT10 fusion as the 3′ segment of KMT2A is oriented to the telomere while the 3′ segment of MLLT10 is oriented to the centromere . Thus, a more complex genomic rearrangement must occur to bring KMT2A and MLLT10 into juxtaposition, and multiple complex 10;11 rearrangements have been described in the literature, and require at least 3 chromosomal breaks to produce the pathogenic 5′ KMT2A /3′ MLLT10 fusion …”

Complex and cryptic chromosomal rearrangements involving the MLL gene in acute leukemia: A study of 7 patients and review of the literature

“…Kowarz et al analyzed three variant t(4;11)(q21;q23) translocations [22]. In all AML-M0 ins(10;11)(p12;q23q13) D MLL-MLLT10 [55] AML-M5 ins(10;11)(p12;q23q13) D MLL-MLLT10 [56] AML-M5b ins(10;11)(p12;q23q23) ND MLL-MLLT10 [57] AML-M5 ins(10;11)(p12;q23q23) ND MLL-MLLT10 [26] ALL ins(10;11)(p12;q23q23) ND MLL-MLLT10 [37] AML-M2 ins(10;11)(p12;q23q23) ND MLL-MLLT10 [55] AML-M5 ins(10;11)(p12;q14q23) ND MLL-MLLT10 [29] AML-M5 ins(10;11)(p12;q23q13) D MLL-MLLT10 [29] BiphenoAL ins(10;11)(p12;q23q13) D MLL-MLLT10 [29] AML-M5a ins(10;11)(p12;q23q13) D MLL-MLLT10 [58] AML-M5 ins(10;11)(p12;q23q12) D MLL-MLLT10 [59] AML-M5 ins(10;11)(p12;q23q21) D MLL-MLLT10 [59] AML-M0 ins(10;11)(p12;q23q13) D MLL-MLLT10 [59] AML-M5 ins(10;11)(p12;q23q23) ND MLL-MLLT10 [28] AML-M5a ins(10;11)(p12;q23q13) D MLL-MLLT10 [28] AML-M5a ins(10;11)(p12;q23q13) D MLL-MLLT10 [28] AML-M5a ins(10;11)(p12;q23q13) D MLL-MLLT10 [28] AML-M5a ins(10;11)(p12;q23q23) ND MLL-MLLT10 [28] AML-M0 ins(10;11)(p12;q23q23) ND MLL-MLLT10 [28] AML-M5a ins(10;11)(p12;q25q23) ND MLL-MLLT10 [60] AML-M2 ins(X;11)(q24;q23q23) ND MLL-SEPT6 [61] AML-M5b inv ins(X;11)(q24;q23q13) D MLL-SEPT6 [62] AML-M2 ins(X;11)(q24;q23q23) ND MLL-SEPT6 [63] AML-M5 ins(9;11)(p21;q23q23) ND MLL-MLLT3 [64] AML-M1 ins ( cases, a MLL-AF4 fusion gene was found. The other two fusion genes resulted in in-frame transcripts in one patient whereas they led to out-of-frame fusion mRNA in a second patient.…”