Acute Undifferentiated Leukemia
editPREVIOUS EDITIONThis page from the 4th edition of Haematolymphoid Tumours is being updated. See 5th edition Table of Contents.
Primary Author(s)*
Amelia Nakanishi, MD and Shashi Shetty, PhD
Cancer Category/Type
Hematologic malignancy/ Acute leukemia
Cancer Sub-Classification / Subtype
Acute Leukemias of Ambiguous Lineage (WHO 2017)/ Acute Undifferentiated Leukemia (AUL)
Definition / Description of Disease
An acute leukemia with blasts that are immunophenotypically ambiguous for any one hematopoietic lineage. AUL is a diagnosis of exclusion that is incompatible with the presence of features that meet the criteria for inclusion in any of the other AML groups (i.e. AML with Recurrent Genetic Abnormalities, AML with Myelodysplasia-Related Changes, or Therapy-Related Myeloid Neoplasms).
To support an undifferentiated phenotype, AUL requires an immunophenotypic work up that “excludes unusual lineages such as plasmacytoid dendritic cell precursors, natural killer precursors, basophils, and non-hematologic cells”[1].
Synonyms / Terminology
Blast cell leukemia, stem cell leukemia, stem cell acute leukemia, undifferentiated leukemia.
Epidemiology / Prevalence
Very rare; precise frequency unknown.
Clinical Features
In one study of 16 cases of adults with AUL, the median age was 63 years (range: 24-84 years) and patients could achieve clinical remission after allogeneic stem cell transplantation[2]. In previous studies that weakly suggest ALL induction regimens over AML induction regimens, there may be selection bias in the patients who were well enough to be transplant candidates[3].
In children, based on limited clinical information in the literature, AUL has been associated with a poor prognosis[4].
Sites of Involvement
Bone marrow and peripheral blood. AUL is so rare, it is unknown if there is a pattern of other sites of involvement.
Morphologic Features
AUL blast morphology is bland and non-specific. Cytoplasmic granulation and disease defining morphology are absent.
Immunophenotype
Per WHO 2017, AUL blasts should express no more than one membrane marker for any lineage.
| Positive (universal) | Precursor stage: HLA-DR, CD34, and/or CD38, CD117, CD133 [5] |
| Positive (subset) | TdT
CD7 (weak positivity) see below. |
| Negative (universal) | Myeloid: MPO
Monocytic: NSE, CD11c, Cd14, CD64, lysozyme, Cd4, CD11b, CD36, NG2 homologue T cell: cCD3 B cell: cCD22, cCD79a, strong CD19 Megakaryocytic: CD41, CD61, CD42, CD235a |
| Negative (subset) | NA |
Additional Description: Blasts are generally positive for HLA-DR, CD34, and/or CD38.
-CD7 positivity is associated with T cells, but can also be seen in some CD34+ hematopoietic stem cells and is not unexpected in a stem cell leukemia[1].
-See HAEM4:Acute Leukemias of Ambiguous Lineage for assigning lineage assignment.
Chromosomal Rearrangements (Gene Fusions)
NA
Characteristic Chromosomal Aberrations / Patterns
AUL is associated with a high rate of chromosomal abnormalities, but have no characteristic abnormalities[2].
Genomic Gain/Loss/LOH
NA
Gene Mutations (SNV/INDEL)
PHF6 a tumor suppressor gene may have implications in AUL though the evidence is limited.
Other Mutations
NA
Epigenomics (Methylation)
Unknown
Genes and Main Pathways Involved
Overexpression of BAALC, ERG, and MN1[1].
Diagnostic Testing Methods
Morphology, immunohistochemistry, cytochemistry, flow cytometry, cytogenetics, and next generation sequencing.
Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)
There is evidence that the genes associated with poor prognosis in acute leukemias, BAALC, ERG, and MN1, are also overexpressed in AUL[1].
Familial Forms
Unknown
Other Information
Although AUL and AML with minimal differentiation are both rare diagnoses, they have similar patient demographics and clinical courses. AUL and AML with minimal differentiation have different molecular abnormalities[2].
Links
HAEM4:Acute Leukemias of Ambiguous Lineage
HAEM5:Mixed-phenotype acute leukaemia, B/myeloid
References
- ↑ 1.0 1.1 1.2 1.3 Borowitz MJ, et al., (2017). Acute leukaemias of ambiguous lineage, 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, p182.
- ↑ 2.0 2.1 2.2 Heesch, Sandra; et al. (2013). "Acute leukemias of ambiguous lineage in adults: molecular and clinical characterization". Annals of Hematology. 92 (6): 747–758. doi:10.1007/s00277-013-1694-4. ISSN 1432-0584. PMID 23412561.
- ↑ Weinberg, Olga K.; et al. (2019). "Clinical, immunophenotypic, and genomic findings of acute undifferentiated leukemia and comparison to acute myeloid leukemia with minimal differentiation: a study from the bone marrow pathology group". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 32 (9): 1373–1385. doi:10.1038/s41379-019-0263-3. ISSN 1530-0285. PMID 31000771.
- ↑ Lee, Hyun Gyung; et al. (2019). "Biphenotypic acute leukemia or acute leukemia of ambiguous lineage in childhood: clinical characteristics and outcome". Blood Research. 54 (1): 63–73. doi:10.5045/br.2019.54.1.63. ISSN 2287-979X. PMC 6439300. PMID 30956966.
- ↑ Hoffman R, et al., (2018) Hematology, basic principles and practice, 7th edition. Elsevier: Philadelphia. (clinical key excerpt)
Notes
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