Mast cell leukemia is an extremely aggressive subtype of

acute myeloid leukemia Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with haematopoiesis, normal blood cell production. Sympto ...

that usually occurs ''de novo'' but can, rarely, evolve from transformation of

chronic myeloid leukemia Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of myeloid cells in the bone marrow and the accumulat ...

into the more aggressive

. In a small proportion of cases, acute mast cell leukemia may evolve from a more progressive form of

systemic mastocytosis Mastocytosis, a type of mast cell disease, is a rare disorder affecting both children and adults caused by the accumulation of functionally defective mast cells (also called ''mastocytes'') and CD34+ mast cell precursors. People affected by mas ...

. The diagnosis of acute mast cell leukemia by the

WHO Who or WHO may refer to: * Who (pronoun), an interrogative or relative pronoun * Who?, one of the Five Ws in journalism * World Health Organization Arts and entertainment Fictional characters * Who, a creature in the Dr. Seuss book ''Horton Hear ...

criteria includes the requirement for a prevalence of 20% neoplastic

mast cells A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granule (cell biology), granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the CFU-GEMM, ...

in marrow and 10% in blood. If the

mast cell A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a pa ...

s represent less than 10% of blood cells, the tumor is called "aleukemic" mast cell leukemia.

Signs and symptoms

Acute mast cell leukemia is a rapidly progressive disorder with leukemic mast cells in blood and in large numbers in marrow. The common signs and symptoms include fever, headache, flushing of face and trunk. The typical cutaneous mast cell infiltrates of urticaria pigmentosa are usually not present before, during, or after diagnosis in patients who have mast cell leukemia. Symptoms include abdominal pain, bone pain, and peptic ulcer which are more prevalent than in other subtypes of

. These former symptoms are due to release of a substance called

histamine Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discovered in ...

from

neoplastic A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

mast cells. Enlargement of the liver and spleen, or

hepatosplenomegaly Hepatosplenomegaly (commonly abbreviated HSM) is the simultaneous enlargement of both the liver (hepatomegaly) and the spleen (splenomegaly). Hepatosplenomegaly can occur as the result of acute viral hepatitis, infectious mononucleosis, and hist ...

is characteristic. The mast cells release also many anticoagulants like

heparin Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the trea ...

which can lead to serious bleeding. Liver and splenic dysfunction also contributes to hemorrhage. Involvement of the bone can lead to osteoporosis. Abdominal

ultrasound Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies fr ...

computerized tomography A computed tomography scan (CT scan; formerly called computed axial tomography scan or CAT scan) is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers ...

(CT) scanning is used to look for hepatosplenomegaly and lymphadenopathy. Plain radiography and bone densitometry can be used to assess bone involvement and the presence of osteoporosis. Endoscopy and biopsy can be useful if gut involvement is suspected.

Diagnosis

Cytochemistry

Cytochemical properties of the leukemic cells must be typical of mast cell derivation (presence of

metachromatic Metachromasia (var. metachromasy) is a characteristical change in the color of staining carried out in biological tissues, exhibited by certain dyes when they bind to particular substances present in these tissues, called chromotropes. For example ...

granules staining with alpha-naphthyl chloroacetate esterase, but not with peroxidase). Mast cell

tryptase Tryptase (, ) is the most abundant secretory granule-derived serine proteinase contained in mast cells and has been used as a marker for mast cell activation. Club cells contain tryptase, which is believed to be responsible for cleaving the hemaggl ...

is an enzyme contained in mast cell granules. Mast cell numbers are best estimated by tryptase immunostaining because very poorly granulated cells may stain very weakly if at all for alpha-naphthol chloroacetate esterase.

Tumor markers

The leukemic cells usually are strongly positive for CD13,

CD33 CD33 or Siglec-3 (sialic acid binding Ig-like lectin 3, SIGLEC3, SIGLEC-3, gp67, p67) is a transmembrane receptor expressed on cells of myeloid lineage. It is usually considered myeloid-specific, but it can also be found on some lymphoid cells. ...

CD68 CD68 ( Cluster of Differentiation 68) is a protein highly expressed by cells in the monocyte lineage (e.g., monocytic phagocytes, osteoclasts), by circulating macrophages, and by tissue macrophages (e.g., Kupffer cells, microglia). Structure ...

, and

CD117 Proto-oncogene c-KIT is the gene encoding the receptor tyrosine kinase protein known as tyrosine-protein kinase KIT, CD117 (cluster of differentiation 117) or mast/stem cell growth factor receptor (SCFR). Multiple transcript variants encoding diff ...

. Characteristically, basophil (e.g.

CD11b Integrin alpha M (ITGAM) is one protein subunit that forms heterodimeric integrin alpha-M beta-2 (αMβ2) molecule, also known as ''macrophage-1 antigen'' (Mac-1) or '' complement receptor 3'' (CR3). ITGAM is also known as CR3A, and cluster of dif ...

CD123 The interleukin-3 receptor ( CD123) is a molecule found on cells which helps transmit the signal of interleukin-3, a soluble cytokine important in the immune system. The gene coding for the receptor is located in the pseudoautosomal region of th ...

) and monocyte markers (

CD14 CD14 (cluster of differentiation 14) is a human protein made mostly by macrophages as part of the innate immune system. It helps to detect bacteria in the body by binding lipopolysaccharide (LPS), a pathogen-associated molecular pattern (PAMP). C ...

CD15 Sialyl LewisX (sLeX), also known as cluster of differentiation 15s (CD15s) or stage-specific embryonic antigen 1 (SSEA-1), is a tetrasaccharide carbohydrate which is usually attached to O-glycans on the surface of cells. It is known to play a vit ...

) are absent. The cells usually express

CD2 CD2 (cluster of differentiation 2) is a cell adhesion molecule found on the surface of T cells and natural killer (NK) cells. It has also been called T-cell surface antigen T11/Leu-5, LFA-2, LFA-3 receptor, erythrocyte receptor and rosette rece ...

and

CD25 Interleukin-2 receptor alpha chain (also called CD25) is the human protein encoded by the ''IL2RA'' gene. The interleukin 2 (IL2) receptor alpha (IL2RA) and beta (IL2RB) chains, together with the common gamma chain (IL2RG), constitute the high-a ...

. Malignant mast cells overexpress the anti-apoptosis gene, bcl-2. A mutation called ''KIT'' mutation is detected in most patients.

Biochemistry

Total serum tryptase is elevated in mast cell leukemia. Normal total (alpha + beta) serum tryptase is approximately 6 micro g/L (range 0 to 11 micro g/L). Values of several hundred micro g/L are characteristic of mast cell leukemia. Plasma and urinary histamine levels are frequently elevated in mast cell leukemia.

Histidine decarboxylase The enzyme histidine decarboxylase (, HDC) is transcribed on chromosome 15, region 21.2, and catalyzes the decarboxylation of histidine to form histamine. In mammals, histamine is an important biogenic amine with regulatory roles in neurotransmis ...

(HDC) is the enzyme that catalyzes the reaction which produces histamine from histidine. Measurement of histidine carboxylase in the marrow cells of patients with mast cell leukemia is a very sensitive marker of mast cells.

Treatment

Immunoglobulin E ( IgE) is important in mast cell function. Immunotherapy with anti-IgE immunoglobulin raised in sheep resulted in a transient decrease in the numbers of circulating mast cells in one patient with mast cell leukemia. Although

splenectomy A splenectomy is the surgical procedure that partially or completely removes the spleen. The spleen is an important organ in regard to immunological function due to its ability to efficiently destroy encapsulated bacteria. Therefore, removal o ...

has led to brief responses in patients with mast cell leukemia, no firm conclusions as to the efficacy of this treatment are possible. Chemotherapy with combination of

cytosine arabinoside Cytarabine, also known as cytosine arabinoside (ara-C), is a chemotherapy medication used to treat acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and non-Hodgkin's lymphoma. It is given by in ...

and either

idarubicin Idarubicin or 4-demethoxydaunorubicin is an anthracycline antileukemic drug. It inserts itself into DNA and prevents DNA unwinding by interfering with the enzyme topoisomerase II. It is an analog of daunorubicin, but the absence of a methoxy gro ...

, daunomycin, or

mitoxantrone Mitoxantrone (INN, BAN, USAN; also known as Mitozantrone in Australia; trade name Novantrone) is an anthracenedione antineoplastic agent. Uses Mitoxantrone is used to treat certain types of cancer, mostly acute myeloid leukemia. It improves the ...

as for acute myeloid leukemia has been used.

Stem cell transplantation Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produ ...

is an option, although no experience exists concerning responses and outcome.

Prognosis

Acute mast cell leukemia is extremely aggressive and has a grave prognosis. In most cases, multi-organ failure including bone marrow failure develops over weeks to months. Median survival after diagnosis is only about 6 months.

References

External links

{{Myeloid malignancy Rare cancers Acute myeloid leukemia