B lymphoblastic leukaemia/lymphoma with KMT2A rearrangement

Haematolymphoid Tumours (WHO Classification, 5th ed.)

editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification

This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:B-Lymphoblastic Leukemia/Lymphoma with t(v;11q23.3); KMT2A-Rearranged.

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Primary Author(s)*

Yassmine Akkari

Nicolas Millan

WHO Classification of Disease

Structure	Disease
Book	Haematolymphoid Tumours (5th ed.)
Category	B-cell lymphoid proliferations and lymphomas
Family	Precursor B-cell neoplasms
Type	B-lymphoblastic leukaemias/lymphomas
Subtype(s)	B lymphoblastic leukaemia/lymphoma with KMT2A rearrangement

Definition / Description of Disease

B lymphoblastic leukemia/ lymphoma is the most common childhood cancer. Despite cure rates exceeding 90%, it remains an important cause of morbidity and mortality in adults and young children, especially when the disease relapses. It is a neoplasm of precursor cells (lymphoblasts) that are committed to the B-cell lineage. Blast cells are small to medium sized, with scant cytoplasm and inconspicuous nucleoli, mostly involving the bone marrow and peripheral blood. Occasionally, however, it can present with involvement of nodal and extra nodal sites (eg. lymph nodes and skin), at which point, it is more accurately referred to as B lymphoblastic lymphoma.

This class of the disease harbors a translocation between the MLL/KMT2A at 11q23 and any one of the large number of fusion partners. Patients with deletions of the MLL/KMT2A locus are not included in this group.

Synonyms / Terminology

MLL = KMT2A

With extensive bone marrow and peripheral blood involvement, B lymphoblastic leukemia is the most appropriate term. If, however, the disease presents as a mass lesion with minimal involvement of the bone marrow and peripheral blood, the term lymphoma should be used. When both sites are involved, the distinction between leukemia and lymphoma is arbitrary. A figure of 25% blasts in the bone marrow is used in some protocols as a threshold for defining leukemia.

Epidemiology / Prevalence

Etiology While the etiology of MLL translocations is unknown, there is strong evidence suggesting that it may occur in utero. These leukemias frequently affect very young infants, and this translocation is sometimes detected in blood spots of patients who later develop the disease. The MLL rearrangement is also seen in 85% of secondary leukemias that occur in patients treated with topoisomerase II inhibitors.

Epidemiology / Prevalence B-LBL/L is primarily a disease of children. 75% of cases occur in children under six years of age. The worldwide incidence is estimated at 1-5/100,000 persons per year.

MLL-rearranged B-ALL is often detected in infant leukemia and accounts for ~2% of all childhood ALLs. The outcome of MLL-R infant ALL remains poor with an event-free survival of 28-36% (Andersson AK et al., 2015 to be quoted in excel sheet). “MLL (mixed-lineage-leukemia) gene rearrangements at 11q23 are present in 80% of all infant B-ALL cases and 10% of all childhood B-ALL [38,39].”

Clinical Features

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Signs and Symptoms	EXAMPLE: Asymptomatic (incidental finding on complete blood counts) EXAMPLE: B-symptoms (weight loss, fever, night sweats) EXAMPLE: Fatigue EXAMPLE: Lymphadenopathy (uncommon)
Laboratory Findings	EXAMPLE: Cytopenias EXAMPLE: Lymphocytosis (low level)

editv4:Clinical Features

The content below was from the old template. Please incorporate above.

A substantial proportion of congenital leukemias, a subset of infant leukemias, harbors a rearrangement of the MLL gene (Moschiano E et al., 2016) MLL rearranged leukemia is associated with certain phenotypic features that distinguish them from other types of leukemia. MLL leukemias tend to be more aggressive, especially in infants, and more frequently present with hyperleukocytosis and central nervous system involvement.

Sites of Involvement

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Morphologic Features

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Immunophenotype

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Finding	Marker
Positive (universal)	EXAMPLE: CD1
Positive (subset)	EXAMPLE: CD2
Negative (universal)	EXAMPLE: CD3
Negative (subset)	EXAMPLE: CD4

Chromosomal Rearrangements (Gene Fusions)

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Chromosomal Rearrangement	Genes in Fusion (5’ or 3’ Segments)	Pathogenic Derivative	Prevalence	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE: t(9;22)(q34;q11.2)	EXAMPLE: 3'ABL1 / 5'BCR	EXAMPLE: der(22)	EXAMPLE: 20% (COSMIC) EXAMPLE: 30% (add reference)	Yes	No	Yes	EXAMPLE: The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).

Individual Region Genomic Gain / Loss / LOH

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Chr #	Gain / Loss / Amp / LOH	Minimal Region Genomic Coordinates [Genome Build]	Minimal Region Cytoband	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE: 7	EXAMPLE: Loss	EXAMPLE: chr7:1- 159,335,973 [hg38]	EXAMPLE: chr7	Yes	Yes	No	EXAMPLE: Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
EXAMPLE: 8	EXAMPLE: Gain	EXAMPLE: chr8:1-145,138,636 [hg38]	EXAMPLE: chr8	No	No	No	EXAMPLE: Common recurrent secondary finding for t(8;21) (add reference).

Characteristic Chromosomal Patterns

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Chromosomal Pattern	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE: Co-deletion of 1p and 18q	Yes	No	No	EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

Gene Mutations (SNV / INDEL)

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Gene; Genetic Alteration	Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)	Prevalence (COSMIC / TCGA / Other)	Concomitant Mutations	Mutually Exclusive Mutations	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE: TP53; Variable LOF mutations EXAMPLE: EGFR; Exon 20 mutations EXAMPLE: BRAF; Activating mutations	EXAMPLE: TSG	EXAMPLE: 20% (COSMIC) EXAMPLE: 30% (add Reference)	EXAMPLE: IDH1 R123H	EXAMPLE: EGFR amplification				EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).

Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

Epigenomic Alterations

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Genes and Main Pathways Involved

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Gene; Genetic Alteration	Pathway	Pathophysiologic Outcome
EXAMPLE: BRAF and MAP2K1; Activating mutations	EXAMPLE: MAPK signaling	EXAMPLE: Increased cell growth and proliferation
EXAMPLE: CDKN2A; Inactivating mutations	EXAMPLE: Cell cycle regulation	EXAMPLE: Unregulated cell division
EXAMPLE:  KMT2C and ARID1A; Inactivating mutations	EXAMPLE:  Histone modification, chromatin remodeling	EXAMPLE:  Abnormal gene expression program

Genetic Diagnostic Testing Methods

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Familial Forms

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Additional Information

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Links

KMT2A

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References

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Notes

*Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome. *Citation of this Page: “B lymphoblastic leukaemia/lymphoma with KMT2A rearrangement”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 09/6/2024, https://ccga.io/index.php/HAEM5:B_lymphoblastic_leukaemia/lymphoma_with_KMT2A_rearrangement.