Mast cell leukemia is an extremely aggressive subtype of
acute myeloid leukemiaAcute myeloid leukemia , also known as acute myelogenous leukemia, is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute...
that usually occurs de novo but can, rarely, evolve from transformation of chronic myeloid leukemia into the more aggressive
acute myeloid leukemiaAcute myeloid leukemia , also known as acute myelogenous leukemia, is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute...
. In a small proportion of cases, acute mast cell leukemia may evolve from a more progressive form of systemic mastocytosis. The diagnosis of acute mast cell leukemia by the
WHO*Who is an English language interrogative pronoun.-In fiction:*Who? , a 1958 novel by science fiction author Algis Budrys, turned into a film with the same title in 1973*Doctor Who, a British science fiction television series...
criteria includes the requirement for a prevalence of 20% neoplastic mast cells in marrow and 10% in blood.
Mast cell leukemia is an extremely aggressive subtype of
acute myeloid leukemiaAcute myeloid leukemia , also known as acute myelogenous leukemia, is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute...
that usually occurs de novo but can, rarely, evolve from transformation of chronic myeloid leukemia into the more aggressive
acute myeloid leukemiaAcute myeloid leukemia , also known as acute myelogenous leukemia, is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute...
. In a small proportion of cases, acute mast cell leukemia may evolve from a more progressive form of systemic mastocytosis. The diagnosis of acute mast cell leukemia by the
WHO*Who is an English language interrogative pronoun.-In fiction:*Who? , a 1958 novel by science fiction author Algis Budrys, turned into a film with the same title in 1973*Doctor Who, a British science fiction television series...
criteria includes the requirement for a prevalence of 20% neoplastic mast cells in marrow and 10% in blood. If the mast cells represent less than 10% of blood cells, the tumor is called "aleukemic" mast cell leukemia.
Cytochemistry
Cytochemical properties of the leukemic cells must be typical of mast cell derivation (presence of metachromatic granules staining with alpha-naphthyl chloroacetate esterase, but not with peroxidase). Mast cell
tryptaseTryptase is the most abundant secretory granule-derived serine proteinase contained in mast cells that has recently been used as a marker for mast cell activation. It is involved with allergenic response and is suspected to act as a mitogen for fibroblast lines...
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,
CD33CD33 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.It binds sialic acids, therefore is a member of the SIGLEC family of lectins.-Structure:...
,
CD68CD68 is a glycoprotein which binds to low density lipoprotein.It is expressed on monocytes/macrophages.The mouse equivalent is called "macrosialin"....
, and
CD117CD117, also called KIT or C-kit receptor, is a cytokine receptor expressed on the surface of hematopoietic stem cells as well as other cell types. This receptor binds to stem cell factor...
. Characteristically, basophil (e.g. CD11b,
CD25CD25 is the alpha chain of the IL-2 receptor. It is a type I transmembrane protein present on activated T cells, activated B cells, some thymocytes, myeloid precursors, and oligodendrocytes that associates with CD122 to form a heterodimer that can act as a high-affinity receptor for IL-2.CD25...
, CD123) and monocyte markers (
CD14Cluster of differentiation 14 also known as CD14 is a human gene.The protein encoded by this gene is a component of the innate immune system. CD14 exists in two forms. It is either anchored into the membrane by a glycosylphosphatidylinositol tail or it appears in a soluble form...
,
CD15CD15 is a cluster of differentiation antigen - an immunologically significant molecule. CD15 is a carbohydrate adhesion molecule that can be expressed on glycoproteins, glycolipids and proteoglycans.- Function :...
) are absent. The cells usually express
CD2CD2 is a cell adhesion molecule found on the surface of T cells and natural killer cells.It has also been called T-cell surface antigen T11/Leu-5, LFA-2, LFA-3 receptor, erythrocyte receptor and rosette receptor....
and
CD25CD25 is the alpha chain of the IL-2 receptor. It is a type I transmembrane protein present on activated T cells, activated B cells, some thymocytes, myeloid precursors, and oligodendrocytes that associates with CD122 to form a heterodimer that can act as a high-affinity receptor for IL-2.CD25...
. 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 decarboxylaseHistidine decarboxylase is the enzyme that catalyzes the reaction that produces histamine from histidine with the help of vitamin B6 as follows:...
(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.
Clinical course
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,
flushingFlushing may refer to:* Flushing , the warm, red condition of human skin* Flush toilet* Flushing , related to skirmishing* Cache flush, when a CPU cache is emptied* Flushing hydrant, a device to flush water mains...
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
acute myeloid leukemiaAcute myeloid leukemia , also known as acute myelogenous leukemia, is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute...
. These former symptoms are due to relase of a substance called
histamineHistamine is a biogenic amine involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by basophils and by...
from neoplastic mast cells. Enlargement of the liver and spleen, or
hepatosplenomegalyHepatosplenomegaly is the simultaneous enlargement of both the liver and the spleen . Hepatosplenomegaly can occur as the result of acute viral hepatitis, infectious mononucleosis or can be the sign of a serious and life threatening lysosomal storage disease.-Common diagnosis:*Farber...
is characteristic. The mast cells release also many anticoagulants like
heparinHeparin, a highly-sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule. It can also be used to form an inner anticoagulant surface on various experimental and medical devices such as test tubes and...
which can lead to serious bleeding. Liver and splenic dysfunction also contributes to hemorrhage. Involvement of the bone can lead to
osteoporosisOsteoporosis is a disease of bone that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is disrupted, and the amount and variety of non-collagenous proteins in bone is altered...
. Abdominal
ultrasoundUltrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Although this limit varies from person to person, it is approximately 20 kilohertz in healthy, young adults and thus, 20 kHz serves as a useful lower limit in describing ultrasound...
or computerized tomography (CT)
scanning should be performed 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.
Therapy
Immunoglobulin E (
IgEIGE is one of the largest MMORPG services companies, with offices in Los Angeles, Miami, and China. IGE is one of the main players in virtual economy services, also known in the MMORPG industry as secondary market...
) 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 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 and either
idarubicinIdarubicin or 4-demethoxydaunorubicin is an anthracycline antileukemic drug that is currently combined with cytosine arabinoside as a first line treatment of acute myeloid leukemia. It belongs to the family of drugs called antitumor antibiotics. FDA approved label can be found . It is distributed...
, daunomycin, or
mitoxantroneMitoxantrone is an Anthracenedione antineoplastic agent.-Uses:It is used in the treatment of certain types of cancer, mostly metastatic breast cancer, acute myeloid leukemia, and non-Hodgkin's lymphoma....
as for acute myeloid leukemia should be considered. Stem cell transplantation 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, multiorgan failure including bone marrow failure develops over weeks to months. Medial survival after diagnosis is only about 6 months.