HAEM4Backup:B-Lymphoblastic Leukemia/Lymphoma with t(v;11q23.3); KMT2A-Rearranged
Primary Author(s)*
Yassmine Akkari
Nicolas Millan
Cancer Category/Type
Precursor Lymphoid neoplasms
Cancer Sub-Classification / Subtype
B lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities: MLL 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
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 |
|---|---|---|---|
| EXAMPLE t(9;22)(q34;q11.2) | EXAMPLE 3'ABL1 / 5'BCR | EXAMPLE der(22) | EXAMPLE 5% |
| EXAMPLE t(8;21)(q22;q22) | EXAMPLE 5'RUNX1 / 3'RUNXT1 | EXAMPLE der(8) | EXAMPLE 5% |
Characteristic Chromosomal Aberrations / Patterns
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Genomic Gain/Loss/LOH
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| Chromosome Number | Gain/Loss/Amp/LOH | Region |
|---|---|---|
| EXAMPLE 8 | EXAMPLE Gain | EXAMPLE chr8:0-1000000 |
| EXAMPLE 7 | EXAMPLE Loss | EXAMPLE chr7:0-1000000 |
Gene Mutations (SNV/INDEL)
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| Gene | Mutation | Oncogene/Tumor Suppressor/Other | Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) | Prevalence (COSMIC/TCGA/Other) |
|---|---|---|---|---|
| EXAMPLE TP53 | EXAMPLE R273H | EXAMPLE Tumor Suppressor | EXAMPLE LOF | EXAMPLE 20% |
Other Mutations
| Type | Gene/Region/Other |
|---|---|
| Concomitant Mutations | EXAMPLE IDH1 R123H |
| Secondary Mutations | EXAMPLE Trisomy 7 |
| Mutually Exclusive | EXAMPLE EGFR Amplification |
Epigenomics (Methylation)
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Genes and Main Pathways Involved
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Diagnostic Testing Methods
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Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)
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Familial Forms
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Other Information
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Links
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References
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EXAMPLE Book
- Arber DA, et al., (2008). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, Editors. IARC Press: Lyon, France, p117-118.
Notes
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