Mast cell leukemia
Encyclopedia
Mast cell leukemia is an extremely aggressive subtype of acute myeloid leukemia
that usually occurs de novo but can, rarely, evolve from transformation of chronic myeloid leukemia into the more aggressive acute myeloid leukemia
. 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
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.
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.
, CD68
, and CD117
. Characteristically, basophil (e.g. CD11b, CD25
, CD123) and monocyte markers (CD14
, CD15
) are absent. The cells usually express CD2
and CD25
. Malignant mast cells overexpress the anti-apoptosis gene, bcl-2. A mutation called KIT mutation is detected in most patients.
(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.
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 leukemia
. These former symptoms are due to release of a substance called histamine
from neoplastic mast cells. Enlargement of the liver and spleen, or hepatosplenomegaly
is characteristic. The mast cells release also many anticoagulants like heparin
which can lead to serious bleeding. Liver and splenic dysfunction also contributes to hemorrhage. Involvement of the bone can lead to osteoporosis
. Abdominal 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.
) 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 idarubicin
, daunomycin, or mitoxantrone
as for acute myeloid leukemia should be considered. Stem cell transplantation is an option, although no experience exists concerning responses and outcome.
Acute myeloid leukemia
Acute 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 leukemia
Acute myeloid leukemia
Acute 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
Who may refer to:* Who , an English-language pronoun* who , a Unix command* Who?, one of the Five Ws in journalism- Art and entertainment :* Who? , a 1958 novel by Algis Budrys...
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
Tryptase is the most abundant secretory granule-derived serine proteinase contained in mast cells that has 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
CD33 or Siglec-3 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....
, CD68
CD68
CD68 is a glycoprotein which binds to low density lipoprotein.It is expressed on monocytes/macrophages.The mouse equivalent is called "macrosialin".-Use in pathology:...
, and CD117
CD117
Mast/stem cell growth factor receptor also known as proto-oncogene c-Kit or tyrosine-protein kinase Kit or CD117 is a protein that in humans is encoded by the KIT gene...
. Characteristically, basophil (e.g. CD11b, CD25
CD25
CD25 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 is...
, CD123) and monocyte markers (CD14
CD14
Cluster 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. Either it is anchored into the membrane by a glycosylphosphatidylinositol tail or it appears in a soluble form...
, CD15
CD15
CD15 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 CD2
CD2
CD2 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 CD25
CD25
CD25 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 is...
. 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
Histidine decarboxylase is the enzyme that catalyzes the reaction that produces histamine from histidine with the help of vitamin B6 as follows:C6H9N3O2 → C5H9N3 + CO2...
(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 (physiology)
For a person to flush is to become markedly red in the face and often other areas of the skin, from various physiological conditions. Flushing is generally distinguished, despite a close physiological relation between them, from blushing, which is milder, generally restricted to the face, cheeks or...
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 leukemia
Acute myeloid leukemia
Acute 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 release of a substance called histamine
Histamine
Histamine is an organic nitrogen compound 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...
from neoplastic mast cells. Enlargement of the liver and spleen, or hepatosplenomegaly
Hepatosplenomegaly
Hepatosplenomegaly is the simultaneous enlargement of both the liver and the spleen . Hepatosplenomegaly can occur as the result of acute viral hepatitis or infectious mononucleosis, or it can be the sign of a serious and life threatening lysosomal storage disease...
is characteristic. The mast cells release also many anticoagulants like heparin
Heparin
Heparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...
which can lead to serious bleeding. Liver and splenic dysfunction also contributes to hemorrhage. Involvement of the bone can lead to osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
. Abdominal ultrasound
Ultrasound
Ultrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...
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
IGE was one of the largest services company buying and selling virtual currencies and accounts for MMORPG. During its peak time, it had offices in Los Angeles, China , and headquarters & customer service centre in Hong Kong. IGE was one of the main monopoly in virtual economy services, also known...
) 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 idarubicin
Idarubicin
Idarubicin or 4-demethoxydaunorubicin is an anthracycline antileukemic drug. It inserts itself into DNA and prevents DNA from unwinding by interfering with the enzyme topoisomerase II. It is an analog of daunorubicin, but the absence of a methoxy group increases its fat solubility and cellular...
, daunomycin, or mitoxantrone
Mitoxantrone
Mitoxantrone 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.