Acute Basophilic Leukemia
Ashwini Yenamandra PhD FACMG
Cancer Sub-Classification / Subtype
Acute Basophilic Leukemia (ABL)
Definition / Description of Disease
Acute basophilic leukemia is a rare subtype of acute myeloid leukemia (AML) with primary differentiation to basophils. This is a distinct entity in the World Health Organization (WHO) classification system within the section of Acute Myeloid Leukemia (AML), Not Otherwise Specified. 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.
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.
Epidemiology / Prevalence
This is a rare disease with a small number of reported cases, accounting for less than 2% of all hematopoietic malignancies.
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.
Sites of Involvement
Bone marrow, Skin
ABL features include immature basophils in the peripheral blood and blast cells with basophilic granules in the bone marrow. These granules show metachromasia when stained with toluidine blue. Identification of the coarse basophilic granules may be the first step in diagnosis of this rare disorder. 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.
Immunophenotyping is positive for myeloid markers such as CD9, CD13, CD33, CD123, CD203c, CD11b and HLA-DR and negative for CD117 in some cases. 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.
|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|
Chromosomal Rearrangements (Gene Fusions)
No consistent chromosomal abnormalities have been reported in ABL due to its rarity. Rearrangement of MYB/GATA1 with t(X;6)(p11;q23) has been reported in four male infants. The fusion gene leads to downregulation of MYB, upregulation of GATA1, and commits myeloid cells to the granulocyte lineage and blocks their differentiation.
|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)|
Characteristic Chromosomal Aberrations / Patterns
Gene Mutations (SNV/INDEL)
Genes and Main Pathways Involved
The molecular mechanism is not completely understood.
Diagnostic Testing Methods
Morphology and IHC.
Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)
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.
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.
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. 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. Immunological markers distinguish between granulated ALL and ABL, and light microscopic cytochemistry for myeloperoxidase and electron microscopy will distinguish ABL from other leukemias.
Put your links here
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