Fei Yang, MD, FACMG, Oregon Health & Science University
Cancer Sub-Classification / Subtype
Definition / Description of Disease
Rare cases of lymphoblastic leukemia/lymphoma express antigens present on NK cells and lack expression of specific markers of T cells, myeloid cells, or plasmacytoid dendritic cells. NK-lymphoblastic leukemia/lymphoma (NK-ALL/LBL) has been very difficult to define, and may be considered in a case that expresses CD56 along with immature T-associated markers such as CD7 and CD2, and even cytoplasmic CD3 in the context of of lacking B-cell and myeloid markers . NK-ALL/LBL is considered as a provisional entity in the current 2016 World Health Organization (WHO) classification system.
Synonyms / Terminology
Epidemiology / Prevalence
The prevalence of NK-Lymphoblastic Leukemia/Lymphoma is not well defined. It is a rare and heterogeneous group of immature disorders suggested to be of precursor NK cell origin.
NK-ALL/LBL patients presented with higher white blood cell and platelet counts compared to other CD56+ hematological disorders .
Sites of Involvement
Bone marrow, lymph node, and extra nodal lesion.
In an early report, the morphologic features were described as immature mononuclear cells intermediate to large in size, with variable cytoplasm and vesicular chromatin .
|Positive (universal)||CD56, CD34, CD2, CD7|
|Positive (subset)||CD33, cCD3, CD5, CD16, CD94|
Chromosomal Rearrangements (Gene Fusions)
Chromosomal rearrangement abnormalities of NK-ALL/LBL are not well defined. The assessment of TCR gene rearrangement is usually negative.
Individual Region Genomic Gain/Loss/LOH
Copy number alterations/Loss of heterozygosity of NK-ALL/LBL are not well defined.
Characteristic Chromosomal Patterns
Chromosomal abnormalities of NK-ALL/LBL are not well defined. In a recent multi-institutional study, complex karyotype has been reported in more than 50% of the NK-ALL/LBL patients .
Gene Mutations (SNV/INDEL)
Genetic abnormalities of NK-ALL/LBL are not well defined. In a recent multi-institutional study, pathogenic mutations were reported common in NOTCH1, ETV6, and JAK3 genes .
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.
Genes and Main Pathways Involved
|Gene; Genetic Alteration||Pathway||Pathophysiologic Outcome|
|ETV6; Inactivating mutations||Transcriptional repressor||Increased cell growth and proliferation|
|NOTCH1; Activating mutations||Signaling transduction||Increased cell differentiation, growth and proliferation|
Diagnostic Testing Methods
Clinical, morphological, and immunophenotypic findings are generally sufficient for diagnosis.
- Borowitz MJ, et al., (2016).T-lymphoblastic leukemia/lymphoma, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4thedition.Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, Editors. IARC Press: Lyon, France, p176-178.
- Weinberg, Olga K.; et al. (2021-07). "Clinical, immunophenotypic and genomic findings of NK lymphoblastic leukemia: a study from the Bone Marrow Pathology Group". Modern Pathology. 34 (7): 1358–1366. doi:10.1038/s41379-021-00739-4. ISSN 1530-0285. Check date values in:
- Sedick, Qanita; et al. (2017-05). "Natural Killer Cell Lymphoblastic Leukaemia/Lymphoma: Case Report and Review of the Recent Literature". Case Reports in Oncology. 10 (2): 588–595. doi:10.1159/000477843. ISSN 1662-6575. PMC 5567073. PMID 28868017. Check date values in:
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- Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p129-171.
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