An hsr on chromosome 7 was shown to be an insertion of four copies of the 11q23 MLL gene region in an HIV-related lymphoma

Reddy, Kavita S.; Parsons, Laura Beth; Mak, Lucia; Chan, Joel A.

doi:10.1016/s0165-4608(01)00438-1

Cited by 4 publications

(6 citation statements)

References 35 publications

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“…MLL rearrangements, excepting rare single case reports of MLL insertions (Garcia-Sanz et al, 1998; Reddy et al, 2001). Two features were immediately apparent from analysis of these data.…”

Section: Discussionmentioning

confidence: 87%

“…Three of the four patients did not reveal any additional information, one patient however presented with 13 unique MLL rearrangements including MLL ‐ MLLT3 , the most commonly observed MLL fusion rearrangement in AML. The patient's diagnosis that required treatment was DLBCL, a disease normally understood to lack MLL rearrangements, excepting rare single case reports of MLL insertions (Garcia‐Sanz et al , ; Reddy et al , ). Two features were immediately apparent from analysis of these data.…”

Section: Discussionmentioning

confidence: 99%

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Multiple clonal MLL fusions in a patient receiving CHOP‐based chemotherapy

et al. 2012

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MLL rearrangements were analysed in the blood of a patient receiving chemotherapy for diffuse large B-cell lymphoma using inverse polymerase chain reaction targeting exon 12, parallel sequencing and a custom algorithm design. Of thirteen MLL rearrangements detected, five were capable of generating MLL fusion genes, including MLL-MLLT3, the most common fusion in acute myeloid leukaemia (AML). Other fusions, all previously clinically unobserved, included MLL-NKD1, a fusion to the negative regulator of Wnt/β-catenin signaling, a pathway linked to leukaemic cell proliferation. The majority of the fusions exhibited clonal persistence from before treatment until six months post-chemotherapy, suggesting the fusions may confer a survival advantage to the mutant clone. MLL breakpoints were partly clustered at a specific location, indicating commonality in the process of their formation. Further, the same MLL breakpoint location exhibited a 50- to 100-fold increase in C to T transitions, consistent with attack by activation-induced cytidine deaminase (AICDA). As is also observed in AML and acute lymphoblastic leukaemia, in this single patient setting, MLL is capable of interacting with multiple fusion partners. This finding defines a discrete site of MLL susceptibility to fragmentation, linked to possible deregulation of AICDA function.

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“…MLL rearrangements, excepting rare single case reports of MLL insertions (Garcia-Sanz et al, 1998; Reddy et al, 2001). Two features were immediately apparent from analysis of these data.…”

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Multiple clonal MLL fusions in a patient receiving CHOP‐based chemotherapy

et al. 2012

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“…The functional consequences of KMT2A translocations in mature B-NHL, including the two DLBCL presented [25]. Two additional reports described KMT2A amplifications in one case each of a plasmablastic lymphoma [10] and an intravascular large B-cell lymphoma [9]. The former exhibited five copies of KMT2A by cytogenetic analysis, occurred in an HIV+ patient and responded to standard chemotherapy [10].…”

Section: Discussionmentioning

confidence: 99%

“…Two additional reports described KMT2A amplifications in one case each of a plasmablastic lymphoma [10] and an intravascular large B-cell lymphoma [9]. The former exhibited five copies of KMT2A by cytogenetic analysis, occurred in an HIV+ patient and responded to standard chemotherapy [10]. Of note, amplifications of the chromosome 11q23 region have been described in intravascular large B-cell lymphomas; however, KMT2A amplification has been confirmed in only one case by FISH analysis [9].…”

Section: Discussionmentioning

confidence: 99%

“…Cytogenetic aberrations of the histone‐lysine N‐methyltransferase 2A ( KMT2A ) gene, previously also referred to as the myeloid lymphoid leukemia/mixed‐lineage leukemia ( MLL ), trithorax‐like protein, CXXC‐type zinc finger protein 7 and zinc finger protein HRX gene, amongst others, have been extensively studied in B‐cell and T‐cell lymphoblastic leukemias, acute myeloid leukemias and myelodysplastic syndromes, where they have been implicated in disease pathogenesis . Although chromosome 11q abnormalities are not infrequent in B‐NHL , little is known about the presence or frequency of KMT2A aberrations and their prognostic impact in these neoplasms, primarily due to the rarity of well documented cases . Here, we describe two unusual extranodal diffuse large B‐cell lymphomas associated with KMT2A translocations, comprising a primary thyroid DLBCL and a large cell transformation of splenic marginal zone lymphoma (SMZL).…”

Section: Introductionmentioning

confidence: 99%

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MLL/KMT2A translocations in diffuse large B‐cell lymphomas

Gindin

Murty

Alobeid

et al. 2014

Hematological Oncology

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Translocations of the histone-lysine N-methyltransferase 2A (KMT2A) gene, formerly known as myeloid lymphoid leukemia/mixed-lineage leukemia gene, are commonly associated with high-risk de novo or therapy-associated B-cell and T-cell lymphoblastic leukemias and myeloid neoplasms. Rare B-cell non-Hodgkin lymphomas harboring KMT2A translocations have been reported, but information regarding the clinical behavior of such cases is limited. Here, we describe two extranodal diffuse large B-cell lymphomas (DLBCLs): a primary thyroid DLBCL and a large cell transformation of a splenic marginal zone lymphoma, which displayed complex karyotypes and translocations involving chromosome 11q23 targeting the KMT2A gene. The pathological and clinical characteristics of these cases are discussed in the context of previously reported lymphomas associated with different types of KMT2A genetic aberrations. In contrast to the poor clinical outcomes of patients with acute leukemias and myeloid neoplasms associated with KMT2A translocations, patients with B-cell non-Hodgkin lymphomas, exhibiting similar translocations, appear to respond well to immunochemotherapy. Our findings add to the growing list of histone methyltransferase genes deregulated in DLBCL and highlight the diversity of mechanisms, altering the function of epigenetic modifier genes in lymphomas.

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