Acute basophilic leukaemia
Haematolymphoid Tumours (WHO Classification, 5th ed.)
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editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition ClassificationThis page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Acute Basophilic Leukemia.
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Primary Author(s)*
Ashwini Yenamandra PhD FACMG
WHO Classification of Disease
| Structure | Disease |
|---|---|
| Book | Haematolymphoid Tumours (5th ed.) |
| Category | Myeloid proliferations and neoplasms |
| Family | Acute myeloid leukaemia |
| Type | Acute myeloid leukaemia, defined by differentiation |
| Subtype(s) | Acute basophilic leukaemia |
Definition / Description of Disease
Acute basophilic leukemia is a rare subtype of acute myeloid leukemia (AML) with primary differentiation to basophils[1]. This is a distinct entity in the World Health Organization (WHO) classification system within the section of HAEM4:Acute Myeloid Leukemia (AML), Not Otherwise Specified[1]. This entity does not 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). Due to the rarity of this disease, consistent genetic diagnostic criteria have not been established. Clinical progression is often rapid and associated with poor prognosis[2].
Synonyms / Terminology
Previously described as “basophilic leukemia”, the 2008 WHO classification of neoplastic diseases was the first edition to define this disorder as a separate entity of unspecified acute myeloid leukemia, now recognized as ABL[1][2][3].
Epidemiology / Prevalence
This is a rare disease with a small number of reported cases, accounting for less than 2% of all hematopoietic malignancies[1].
Clinical Features
Put your text here and fill in the table (Instruction: Can include references in the table. Do not delete table.)
| 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 FeaturesThe content below was from the old template. Please incorporate above.Clinical features include bone marrow failure and may or may not have circulating blasts. Cutaneous involvement, oraganomegaly, lytic lesions and symptoms related to hyperhistanemia may be present[1].
Sites of Involvement
Bone marrow, Skin
Morphologic Features
ABL features include immature basophils in the peripheral blood and blast cells with basophilic granules in the bone marrow[1][2]. These granules show metachromasia when stained with toluidine blue[1][2]. Identification of the coarse basophilic granules may be the first step in diagnosis of this rare disorder[1][2][4][5]. Blasts are usually negative with Sudan Black B (SBB), myeloperoxidase (MPO), and neuron–specific enolase (NSE). Diffuse staining with acid phosphatase and peroxidase activity may be present in some cases[1].
Immunophenotype
Immunophenotyping is positive for myeloid markers such as CD9, CD13, CD33, CD123, CD203c, CD11b and HLA-DR and negative for CD117 in some cases[1]. The blasts may stain positive for toluidine blue, PAS, acid phosphatase, and myeloperoxidase. Immunophenotyping and electron microscopy may also identify a basophilic lineage; this is especially crucial to differentiate basophilic cells from closely related mast cells.
| Finding | Marker |
|---|---|
| Positive (universal) | CD13, CD33, CD34, Class II HLA-DR |
| Positive (subset) | Mature basophils can be CD25+ and CD117-, mast cells can be CD117+ and CD25+, blasts can be CD9+ and TdT+. |
| Negative (universal) | No B or T -lymphoid markers |
| Negative (subset) | CD117 |
Chromosomal Rearrangements (Gene Fusions)
Put your text here and fill in the table
| 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). |
editv4:Chromosomal Rearrangements (Gene Fusions)The content below was from the old template. Please incorporate above.No consistent chromosomal abnormalities have been reported in ABL due to its rarity[6][7][8]. Rearrangement of MYB/GATA1 with t(X;6)(p11;q23) has been reported in four male infants[7][8]. The fusion gene leads to downregulation of MYB, upregulation of GATA1, and commits myeloid cells to the granulocyte lineage and blocks their differentiation[7][8].
Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Pathogenic Derivative Prevalence t(X;6)(p11;q23) 5'MYB / 3'GATA1 der(X) Rare (4 cases)
editv4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).Please incorporate this section into the relevant tables found in:
- Chromosomal Rearrangements (Gene Fusions)
- Individual Region Genomic Gain/Loss/LOH
- Characteristic Chromosomal Patterns
- Gene Mutations (SNV/INDEL)
Diagnosis of this disease may allow for appropriate prophylactic measures, including H1 and H2 blockers and proton pump inhibitors and steroids, to be initiated in an attempt to minimize its protean complications[1].
This disease is prognostically unfavorable and may have unique therapeutic complications, including anaphylaxis and life threatening cardiac involvement. A low remission rate and short survival are characteristic of ABL[1][6][7].
Individual Region Genomic Gain / Loss / LOH
Put your text here and fill in the table (Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable. Do not delete table.)
| 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). |
editv4:Genomic Gain/Loss/LOHThe content below was from the old template. Please incorporate above.Not applicable.
Characteristic Chromosomal Patterns
Put your text here (EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis. Do not delete table.)
| 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). |
editv4:Characteristic Chromosomal Aberrations / PatternsThe content below was from the old template. Please incorporate above.A few male patients have been reported with massive hyperdiploid or tetraploid karyotypes[2][3][6][9]. Monosomy 7 was reported in a rare case[10].
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.
editv4:Gene Mutations (SNV/INDEL)The content below was from the old template. Please incorporate above.Not applicable.
Other Mutations
Not applicable.
Epigenomic Alterations
Not applicable.
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 |
editv4:Genes and Main Pathways InvolvedThe content below was from the old template. Please incorporate above.The molecular mechanism is not completely understood.
Genetic Diagnostic Testing Methods
Morphology and IHC.
Familial Forms
Not applicable.
Additional Information
Differential Diagnosis - The differential diagnosis includes blast phase of MPN, other subtypes of AML with basophilia such as AML with t(6;9) (p23;q34), mast cell leukemia and a subtype of ALL with course granules[1]. The clinical features and cytogenetic pattern will distinguish cases presenting de novo from cases that result from transformation of chronic myelogenous leukemia and other subtypes of AML with basophilia[1]. Immunological markers distinguish between granulated ALL and ABL, and light microscopic cytochemistry for myeloperoxidase and electron microscopy will distinguish ABL from other leukemias[1].
Links
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References
(use the "Cite" icon at the top of the page) (Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference.)
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 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. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. IARC Press: Lyon, France, p164-165.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Kritharis, Athena; et al. (2011). "Acute basophilic leukemia associated with loss of gene ETV6 and protean complications". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 29 (21): e623–626. doi:10.1200/JCO.2010.34.5710. ISSN 1527-7755. PMID 21576634.
- ↑ 3.0 3.1 Duchayne, E.; et al. (1999). "Diagnosis of acute basophilic leukemia". Leukemia & Lymphoma. 32 (3–4): 269–278. doi:10.3109/10428199909167387. ISSN 1042-8194. PMID 10037024.
- ↑ Iyer, Renuka V.; et al. (2004). "Massive hyperdiploidy and tetraploidy in acute myelocytic leukemia and myelodysplastic syndrome". Cancer Genetics and Cytogenetics. 148 (1): 29–34. doi:10.1016/s0165-4608(03)00214-0. ISSN 0165-4608. PMID 14697638.
- ↑ Béné, M.-C.; et al. (2006). "Near-tetraploid acute myeloid leukemias: an EGIL retrospective study of 25 cases". Leukemia. 20 (4): 725–728. doi:10.1038/sj.leu.2404110. ISSN 0887-6924. PMID 16437146.
- ↑ 6.0 6.1 6.2 Yenamandra A, et al., (2014). Acute basophilic leukemia, a rare subset of de novo AML with an abnormal tetraploid karyotype. JSM Cell Dev Biol 2(1):1007. Available online at https://www.academia.edu/28924195/Editorial_Article_Acute_Basophilic_Leukemia_a_Rare_Subset_of_De_Novo_AML_with_an_Abnormal_Tetraploid_Karyotype.
- ↑ 7.0 7.1 7.2 7.3 Dastugue, N.; et al. (1997). "Acute basophilic leukaemia and translocation t(X;6)(p11;q23)". British Journal of Haematology. 98 (1): 170–176. doi:10.1046/j.1365-2141.1997.1562968.x. ISSN 0007-1048. PMID 9233581.
- ↑ 8.0 8.1 8.2 Quelen, Cathy; et al. (2011). "Identification of a transforming MYB-GATA1 fusion gene in acute basophilic leukemia: a new entity in male infants". Blood. 117 (21): 5719–5722. doi:10.1182/blood-2011-01-333013. ISSN 1528-0020. PMID 21474671.
- ↑ Kim, Bo Hyun; et al. (2013). "Two cases of near-tetraploidy in acute leukemias of ambiguous lineage". Annals of Laboratory Medicine. 33 (5): 371–374. doi:10.3343/alm.2013.33.5.371. ISSN 2234-3814. PMC 3756245. PMID 24003431.
- ↑ Shin, So Youn; et al. (2007). "Monosomy 7 as the sole abnormality of an acute basophilic leukemia". Cancer Genetics and Cytogenetics. 172 (2): 168–171. doi:10.1016/j.cancergencyto.2006.09.016. ISSN 0165-4608. PMID 17213028.
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: “Acute basophilic leukaemia”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 09/6/2024, https://ccga.io/index.php/HAEM5:Acute_basophilic_leukaemia.