KMT2A (MLL) rearrangements observed in pediatric/young adult T-lymphoblastic leukemia/lymphoma: A 10-year review from a single cytogenetic laboratory

Jess F. Peterson, Linda Baughn, Kathryn E. Pearce, Cynthia M. Williamson, Jonna C. Benevides Demasi, Renee M. Olson, Tony A. Goble, Reid G. Meyer, Patricia T Greipp, Rhett P. Ketterling

Research output: Contribution to journalArticle

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Abstract

T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) accounts for approximately 15% of pediatric and 25% of adult ALL. While the underlying frequency of KMT2A (MLL) gene rearrangements has been identified in approximately 4-8% of T-ALL/LBL cases, a paucity of literature is available to characterize further the KMT2A rearrangements in pediatric/young adult T-ALL/LBL. A 10-year retrospective review was performed to identify KMT2A rearrangements in specimens sent for T-ALL/LBL fluorescence in situ hybridization studies in patients under the age of 30 years. Of 806 T-ALL/LBL FISH studies performed on unique individuals, 27 (3.3%) harbored KMT2A rearrangements. Nineteen patients were male and eight were female (M:F ratio, 2.4:1) with ages ranging from 1 to 20 years (mean 12, median 12). Of the 27 cases, nine (33%) had KMT2A/MLLT1 fusions, eight (30%) had KMT2A/AFDN fusions, two (7%) had KMT2A/ELL fusions, and one (4%) had a KMT2A/MLLT10 fusion. In addition, five (19%) had KMT2A rearrangements with unidentified gene fusion partners and two (7%) had 3’KMT2A deletions. Our results indicate that MLLT1 and AFDN account for the majority (63%) of KMT2A gene partners in pediatric/young adult T-ALL/LBL, while no KMT2A/AFF1 or KMT2A/MLLT3 fusions were observed despite their common identification in B-ALL and acute myeloid leukemia, respectively. In addition to diagnostic and prognostic value, detecting specific KMT2A fusions may also be of clinical importance in the era of targeted therapies.

Original languageEnglish (US)
JournalGenes Chromosomes and Cancer
DOIs
StateAccepted/In press - Jan 1 2018

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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
antineoplaston A10
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Cytogenetics
Young Adult
Pediatrics
Gene Rearrangement
Gene Fusion
Fluorescence In Situ Hybridization
Acute Myeloid Leukemia
Genes

Keywords

  • Chromosome analysis
  • Fluorescence in situ hybridization (FISH)
  • KMT2A MLL
  • T-lymphoblastic leukemia/lymphoma (T-ALL/LBL)

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Cite this

KMT2A (MLL) rearrangements observed in pediatric/young adult T-lymphoblastic leukemia/lymphoma : A 10-year review from a single cytogenetic laboratory. / Peterson, Jess F.; Baughn, Linda; Pearce, Kathryn E.; Williamson, Cynthia M.; Benevides Demasi, Jonna C.; Olson, Renee M.; Goble, Tony A.; Meyer, Reid G.; Greipp, Patricia T; Ketterling, Rhett P.

In: Genes Chromosomes and Cancer, 01.01.2018.

Research output: Contribution to journalArticle

Peterson, Jess F. ; Baughn, Linda ; Pearce, Kathryn E. ; Williamson, Cynthia M. ; Benevides Demasi, Jonna C. ; Olson, Renee M. ; Goble, Tony A. ; Meyer, Reid G. ; Greipp, Patricia T ; Ketterling, Rhett P. / KMT2A (MLL) rearrangements observed in pediatric/young adult T-lymphoblastic leukemia/lymphoma : A 10-year review from a single cytogenetic laboratory. In: Genes Chromosomes and Cancer. 2018.
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abstract = "T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) accounts for approximately 15{\%} of pediatric and 25{\%} of adult ALL. While the underlying frequency of KMT2A (MLL) gene rearrangements has been identified in approximately 4-8{\%} of T-ALL/LBL cases, a paucity of literature is available to characterize further the KMT2A rearrangements in pediatric/young adult T-ALL/LBL. A 10-year retrospective review was performed to identify KMT2A rearrangements in specimens sent for T-ALL/LBL fluorescence in situ hybridization studies in patients under the age of 30 years. Of 806 T-ALL/LBL FISH studies performed on unique individuals, 27 (3.3{\%}) harbored KMT2A rearrangements. Nineteen patients were male and eight were female (M:F ratio, 2.4:1) with ages ranging from 1 to 20 years (mean 12, median 12). Of the 27 cases, nine (33{\%}) had KMT2A/MLLT1 fusions, eight (30{\%}) had KMT2A/AFDN fusions, two (7{\%}) had KMT2A/ELL fusions, and one (4{\%}) had a KMT2A/MLLT10 fusion. In addition, five (19{\%}) had KMT2A rearrangements with unidentified gene fusion partners and two (7{\%}) had 3’KMT2A deletions. Our results indicate that MLLT1 and AFDN account for the majority (63{\%}) of KMT2A gene partners in pediatric/young adult T-ALL/LBL, while no KMT2A/AFF1 or KMT2A/MLLT3 fusions were observed despite their common identification in B-ALL and acute myeloid leukemia, respectively. In addition to diagnostic and prognostic value, detecting specific KMT2A fusions may also be of clinical importance in the era of targeted therapies.",
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AU - Pearce, Kathryn E.

AU - Williamson, Cynthia M.

AU - Benevides Demasi, Jonna C.

AU - Olson, Renee M.

AU - Goble, Tony A.

AU - Meyer, Reid G.

AU - Greipp, Patricia T

AU - Ketterling, Rhett P.

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AB - T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) accounts for approximately 15% of pediatric and 25% of adult ALL. While the underlying frequency of KMT2A (MLL) gene rearrangements has been identified in approximately 4-8% of T-ALL/LBL cases, a paucity of literature is available to characterize further the KMT2A rearrangements in pediatric/young adult T-ALL/LBL. A 10-year retrospective review was performed to identify KMT2A rearrangements in specimens sent for T-ALL/LBL fluorescence in situ hybridization studies in patients under the age of 30 years. Of 806 T-ALL/LBL FISH studies performed on unique individuals, 27 (3.3%) harbored KMT2A rearrangements. Nineteen patients were male and eight were female (M:F ratio, 2.4:1) with ages ranging from 1 to 20 years (mean 12, median 12). Of the 27 cases, nine (33%) had KMT2A/MLLT1 fusions, eight (30%) had KMT2A/AFDN fusions, two (7%) had KMT2A/ELL fusions, and one (4%) had a KMT2A/MLLT10 fusion. In addition, five (19%) had KMT2A rearrangements with unidentified gene fusion partners and two (7%) had 3’KMT2A deletions. Our results indicate that MLLT1 and AFDN account for the majority (63%) of KMT2A gene partners in pediatric/young adult T-ALL/LBL, while no KMT2A/AFF1 or KMT2A/MLLT3 fusions were observed despite their common identification in B-ALL and acute myeloid leukemia, respectively. In addition to diagnostic and prognostic value, detecting specific KMT2A fusions may also be of clinical importance in the era of targeted therapies.

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KW - T-lymphoblastic leukemia/lymphoma (T-ALL/LBL)

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