HAEM4Backup:NK-Lymphoblastic Leukemia/Lymphoma

Primary Author(s)*

Fei Yang, MD, FACMG, Oregon Health & Science University

Cancer Category/Type

T-Lymphoblastic Leukemia (T-ALL)

Cancer Sub-Classification / Subtype

NK-Lymphoblastic Leukemia/Lymphoma

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

N/A

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.

Clinical Features

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.

Morphologic Features

In an early report, the morphologic features were described as immature mononuclear cells intermediate to large in size, with variable cytoplasm and vesicular chromatin .

Immunophenotype

Finding	Marker
Positive (universal)	CD56, CD34, CD2, CD7
Positive (subset)	CD33, cCD3, CD5, CD16, CD94
Negative (universal)	N/A
Negative (subset)	N/A

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.

Epigenomic Alterations

N/A

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.

Familial Forms

Unknown

Additional Information

N/A

Links

N/A

References

(use "Cite" icon at top of page)

EXAMPLE Book

1. 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.

Notes

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