Acute monocytic leukemia
Encyclopedia
Acute monocytic leukemia (AMoL, or AML-M5) is considered a type of acute myeloid leukemia
.
(WHO) criteria for AML-5, a patient must have greater than 20% blasts in the bone marrow
, and of these, greater than 80% must be of the monocytic
lineage. A further subclassification (M5a versus M5b) is made depending on whether the monocytic cells are predominantly monoblast
s (>80%) (acute monoblastic leukemia) or a mixture of monoblasts and promonocyte
s (<80% blasts). Monoblasts can be distinguished by having a roughly circular nucleus
, delicate lacy chromatin
, and abundant, often basophilic cytoplasm
. These cells may also have pseudopod
s. By contrast, promonocytes have a more convoluted nucleus, and their cytoplasm may contain metachromatic granules. Monoblasts are typically MPO
-negative and promonocytes are MPO variable. Both monoblasts and promonocytes stain positive for non-specific esterase (NSE), however NSE may often be negative.
Immunophenotypically, M5-AML variably express myeloid (CD13, CD33
) and monocytic (CD11b, CD11c
) markers. Cells may aberrantly express B-cell marker CD20
and the NK marker CD56. Monoblasts may be positive for CD34
.
at 11q23 or t(9;11) affecting the MLL
locus, however the MLL translocation is also found in other AML subtypes. MLL is believed to be prognostically unfavorable in AML-M5 compared to other genetic alterations involving MLL such as t(9;11). The t(8;16) translocation in MLL is associated with hemophagocytosis
.
AML-M5 is thought to be associated with exposure to Epipodophyllotoxin
.
(such as anthracyclines) or with bone marrow transplantation.
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...
.
Diagnosis
In order to fulfill World Health OrganizationWorld Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
(WHO) criteria for AML-5, a patient must have greater than 20% blasts in the bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
, and of these, greater than 80% must be of the monocytic
Monocyte
Monocytes are a type of white blood cell and are part of the innate immune system of vertebrates including all mammals , birds, reptiles, and fish. Monocytes play multiple roles in immune function...
lineage. A further subclassification (M5a versus M5b) is made depending on whether the monocytic cells are predominantly monoblast
Monoblast
Monoblasts are normally found in bone marrow and do not appear in the normal peripheral blood. They mature into monocytes which, in turn, develop into macrophages.-Structure:...
s (>80%) (acute monoblastic leukemia) or a mixture of monoblasts and promonocyte
Promonocyte
A promonocyte is a cell arising from a monoblast and developing into a monocyte.-External links:* * - "Bone marrow smear"*...
s (<80% blasts). Monoblasts can be distinguished by having a roughly circular nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
, delicate lacy chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...
, and abundant, often basophilic cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
. These cells may also have pseudopod
Pseudopod
Pseudopods or pseudopodia are temporary projections of eukaryotic cells. Cells that possess this faculty are generally referred to as amoeboids. Pseudopodia extend and contract by the reversible assembly of actin subunits into microfilaments...
s. By contrast, promonocytes have a more convoluted nucleus, and their cytoplasm may contain metachromatic granules. Monoblasts are typically MPO
Myeloperoxidase
Myeloperoxidase is a peroxidase enzyme that in humans is encoded by the MPO gene. Myeloperoxidase is most abundantly expressed in neutrophil granulocytes . It is a lysosomal protein stored in azurophilic granules of the neutrophil...
-negative and promonocytes are MPO variable. Both monoblasts and promonocytes stain positive for non-specific esterase (NSE), however NSE may often be negative.
Immunophenotypically, M5-AML variably express myeloid (CD13, CD33
CD33
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....
) and monocytic (CD11b, CD11c
CD11c
CD11c, also known as Integrin, alpha X , is a human gene.CD11c is a type I transmembrane protein found at high levels on most human dendritic cells, but also on monocytes, macrophages, neutrophils, and some B cells that induces cellular activation and helps trigger neutrophil respiratory burst;...
) markers. Cells may aberrantly express B-cell marker CD20
CD20
B-lymphocyte antigen CD20 or CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all B-cells beginning at the pro-B phase and progressively increasing in concentration until maturity....
and the NK marker CD56. Monoblasts may be positive for CD34
CD34
CD34 molecule is a cluster of differentiation molecule present on certain cells within the human body. It is a cell surface glycoprotein and functions as a cell-cell adhesion factor. It may also mediate the attachment of stem cells to bone marrow extracellular matrix or directly to stromal cells...
.
Causes
M5 is associated with characteristic chromosomal abnormalities, often involving Chromosome 11Chromosome 11 (human)
thumb|right|Chromosome 11 ChartChromosome 11 is one of the 23 pairs of chromosomes in humans. Humans normally have two copies of this chromosome. Chromosome 11 spans about 134.5 million base pairs and represents between 4 and 4.5 percent of the total DNA in cells...
at 11q23 or t(9;11) affecting the MLL
MLL (gene)
Histone-lysine N-methyltransferase HRX is an enzyme that in humans is encoded by the MLL gene.MLL is a histone methyltransferase deemed a positive global regulator of gene transcription...
locus, however the MLL translocation is also found in other AML subtypes. MLL is believed to be prognostically unfavorable in AML-M5 compared to other genetic alterations involving MLL such as t(9;11). The t(8;16) translocation in MLL is associated with hemophagocytosis
Hemophagocytosis
Hemophagocytosis is phagocytosis by histiocytes of erythrocytes, leukocytes, platelets, and their precursors in bone marrow and other tissues.It is part of the presentation of hemophagocytic lymphohistiocytosis....
.
AML-M5 is thought to be associated with exposure to Epipodophyllotoxin
Epipodophyllotoxin
Epipodophyllotoxins are alkaloids naturally occurring in the root of American Mayapple plant .Some epipodophyllotoxin derivatives are currently used in the treatment of cancer. These include etoposide and teniposide. They act as anti-cancer drugs by inhibiting topoisomerase II....
.
Treatment
AML-M5 is treated with intensive chemotherapyChemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
(such as anthracyclines) or with bone marrow transplantation.
External links
- Images at Nagoya UniversityNagoya UniversityNagoya University is one of the most prestigious universities in Japan. It can be seen in the several rankings such as shown below.-General Rankings:...
- Image at hmds.org.uk
- Histology at University of VirginiaUniversity of VirginiaThe University of Virginia is a public research university located in Charlottesville, Virginia, United States, founded by Thomas Jefferson...
- Overview at Marist CollegeMarist CollegeMarist College is a private liberal arts college on the east bank of the Hudson River near Poughkeepsie, New York. The site was established in 1905 by Marist Brothers, and the college was chartered in 1929...