Identification of MLL partner genes in 27 patients with acute leukemia from a single cytogenetic laboratory

Abstract

Chromosomal rearrangements involving the MLL gene have been associated with many different types of hematological malignancies. Fluorescent in situ hybridization with a panel of probes coupled with long distance inverse-PCR was used to identify chromosomal rearrangements involving the MLL gene. Between 1995 and 2010, 27 patients with an acute leukemia were found to have a fusion gene involving MLL. All seven ALL patients with B cell acute lymphoblastic leukemia were characterized by the MLL/AFF1 fusion gene resulting from a translocation (5 patients) or an insertion (2 patients). In the 19 AML patients with acute myeloblastic leukemia, 31.6% of all characterized MLL fusion genes were MLL/MLLT3, 21.1% MLL/ELL, 10.5% MLL/MLLT6 and 10.5% MLL/EPS15. Two patients had rare or undescribed fusion genes, MLL/KIAA0284 and MLL/FLNA. Seven patients (26%) had a complex chromosomal rearrangement (three-way translocations, insertions, deletions) involving the MLL gene. Splicing fusion genes were found in three patients, leading to a MLL/EPS15 fusion in two and a MLL/ELL fusion in a third patient. This study showed that fusion involving the MLL gene can be generated through various chromosomal rearrangements such as translocations, insertions and deletions, some being complex or cryptic. A systematic approach should be used in all cases of acute leukemia starting with FISH analyses using a commercially available MLL split signal probe. Then, the analysis has to be completed, if necessary, by further molecular cytogenetic and genomic PCR methods.

The incidence and distribution characteristics of MLL rearrangements in Chinese acute myeloid leukemia patients by multiplex nested RT-PCR

“…In our study, MLL-AF9 occurred with the second highest frequency in acute myeloid leukemia, after MLL-PTD which occurred with the highest frequency. [28]. In our study, among 68 AML patients with MLL rearrangements, there was a 14.7% incidence of MLL-ELL.…”

Cytogenetic and Molecular Findings in Children with Acute Lymphoblastic Leukemia: Experience of a Single Institution in Argentina

“…Therefore, our results confirm, as other authors have suggested, that the break apart dual color FISH probe is the most appropriate method to detect KMT2A rearrangements; it also detects 3 ′ deletions and cryptic insertions. FISH for evaluation of KMT2A rearrangements should be used in all cases of acute leukemia with a normal karyotype or in those cases with suspected 11q23 abnormalities, and if necessary, further molecular cytogenetic and genomic PCR methods should be used [De Braekeleer et al, 2011].…”

Complex Three-Way Translocation Involving <b><i>MLL</i></b>, <b><i>ELL</i></b>, <b><i>RREB1</i></b>, and <b><i>CMAHP </i></b>Genes in an Infant with Acute Myeloid Leukemia and t(6;19;11)(p22.2;p13.1;q23.3)

“…More 13 than 100 MLL rearrangements are known and 64 of these translocation partner genes are characterized at the molecular level [Balgobind et al, 2009;Meyer et al, 2009;De Braekeleer et al, 2011]. The MLL gene is translocated and/or rearranged more frequently in infant leukemias than in leukemias in older children and in adults.…”