Acute myelomonocytic leukemia (AMML) is a form 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 normal blood cell production. Symptoms may includ ...

that involves a proliferation of

CFU-GM CFU-GM, also known as granulocyte–macrophage progenitor (GMP), is a colony forming unit. It is derived from CFU-GEMM. The "GM" stands for "granulocyte, monocyte". It is the precursor for monoblasts and myeloblasts. Production is stimulated by ...

myeloblast The myeloblast is a unipotent stem cell which differentiates into the effectors of the granulocyte series. It is found in the bone marrow. Stimulation of myeloblasts by G-CSF and other cytokines triggers maturation, differentiation, proliferation a ...

s and

monoblast Monoblasts are the committed progenitor cells that differentiated from a committed macrophage or dendritic cell precursor (MDP) in the process of hematopoiesis. They are the first developmental stage in the monocyte series leading to a macrophage. ...

s. AMML occurs with a rapid increase amount in white blood cell count and is defined by more than 20% of myeloblast in the bone marrow. It is classified under "M4" in the French-American-British classification (FAB). It is classified under "AML, not otherwise classified" in the WHO classification. Translocations have been observed. Progression from

myelodysplastic syndrome A myelodysplastic syndrome (MDS) is one of a group of cancers in which immature blood cells in the bone marrow do not mature, and as a result, do not develop into healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may ...

has been reported.

Signs and symptoms

Some patients may experience: *Fatigue *Easy Bruising *Abnormal Bleeding *Anemia *

Thrombocytopenia Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients an ...

Dyspnea Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathing, breathe well enough. The American Thoracic Society defines it as "a subjective experience of brea ...

If the blast count gets too high and clog up blood vessels, some patients may experience: *Slurred Speech *Headache *Confusion *Weakness on one side of the body *Sleepiness

Cause

The cause has not yet been determined. It has been said that acute myeloid leukemia can occur from a progression of chronic myelomonocytic leukemia type 1 and 2. Normal red blood cells decrease and a rapid proliferation of the abnormal myeloblasts occur.

Apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

functional ability decreases which causes a back up of myeloblasts in the bone marrow and blood. AML with a translocation or inversion is seen in different chromosomes. Specifically, AML with inversion in chromosome 16 also known as inv(16) is commonly seen in children.

Mechanism

AMML does not have an exact mechanism. The underlying pathophysiology of acute myeloid leukemia consist of maturational arrest of the bone marrow cell during the early stages of development. A myeloblast is an immature precursor cell that will change into a monocyte, healthy white blood cell. In AML, Myeloblast do not mature but grow and multiply with regulation. The abnormal cells build up in the bone marrow and prevent the development of other healthy cells. This type of arrest is still under study but in most cases, a gene inactivation or activation has occurred due to chromosome translocations or inversion. AML-M4 with an inversion of chromosome 16 is caused by breakage and rearrangement within itself.

Diagnosis

Criteria for AMML is confirmed if the myeloblasts and

promonocyte A promonocyte (or premonocyte) is a cell arising from a monoblast and developing into a monocyte. See also * Pluripotential hemopoietic stem cell Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This proc ...

s in the bone marrow are greater than 20 percent. It can also be confirmed if the blood monocytes is 5x10⁹/L or higher. Testing available to diagnosis AML includes a complete blood count which is characterized by blood that is taken from the vein in the arm to test for leukemia, a peripheral blood smear and a bone marrow test. During a peripheral blood smear, a sample of blood is checked for blast cells, white blood cell count and changes in shape of blood cells. During a bone marrow test, bone marrow is taken from the hip bone in a search for leukemia cells. Aspiration and biopsy are two types of testing that can be done in order to obtain bone marrow. Further classification can be done for the type of AML by examining the cell's shape and size. Generally you'll find immature cells which lack normal features of a cell.

Treatment

AMML can be treated depending on the degree of disease, age of patient, and current patient's health status. Treatment consists of a multi-drug chemotherapy regimen.Verschuur, A. C. (2004, May). Acute myelomonocytic leukemia. Retrieved December 13, 2019, from https://www.orpha.net/data/patho/Pro/en/AcuteMyelomonocyticLeukemia-FRenPro8560.pdf. Chemotherapy drugs often used to treat AML are

cytarabine 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 an

anthracycline Anthracyclines are a class of drugs used in cancer chemotherapy that are extracted from ''Streptomyces'' bacterium. These compounds are used to treat many cancers, including leukemias, lymphomas, breast, stomach, uterine, ovarian, bladder cance ...

drug. Chemotherapy is broken down into 2 phases: * Induction therapy: first short and invasive phase of treatment with the goal to the blood of blasts and reduce the number of blasts in the bone marrow back to normal. * Consolidation therapy: second phase given in cycles that occur after the patient has recovered from induction therapy. Its objective is to kill remaining blasts that can't be seen. In some cases, an allogenic bone marrow transplantation can be performed. If AML with chromosomal abnormalities such as inv(16) are often cured by the standard chemotherapy regimen.

Prognosis

With AMML being difficult to fully treat, the five-year survival rate is about 38-72% which typically decrease to 35-60% if there's no bone marrow transplantation performed. Generally older patients over 60 have a poor outlook due to prior health status before the diagnosis and the aggressive chemotherapy regimen used. The aggressive chemotherapy regimen can lead to long-term side effects such as prolonged anemia,

leukocytopenia Leukopenia () is a decrease in the number of leukocytes (WBC). Found in the blood, they are the white blood cells, and are the body's primary defense against an infection. Thus the condition of leukopenia places individuals at increased risk of inf ...

neutropenia Neutropenia is an abnormally low concentration of neutrophils (a type of white blood cell) in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria ...

, and

thrombocytopenia Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients an ...

. The use of anthracycline drugs can cause a decrease in cardiac contractility, both short and long term. Those with AML-M4 inv(16) have a favorable prognosis with a five-year overall survival rate of 61%.

Epidemiology

AML is commonly seen in pediatric patients with higher pediatric incidence in Hispanics and Asians as compared to non-Hispanic Caucasian and African Americans in the USA. Predisposition to AML includes but not limited to:

Down syndrome Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is usually associated with physical growth delays, mild to moderate intellectual dis ...

Klinefelter's syndrome Klinefelter syndrome (KS), also known as 47,XXY, is an aneuploid genetic condition where a male has an additional copy of the X chromosome. The primary features are infertility and small, poorly functioning testicles. Usually, symptoms are subt ...

, and

Fanconi's anemia Fanconi anaemia (FA) is a rare Genetic disorder, genetic disease resulting in impaired response to DNA damage. Although it is a very rare disorder, study of this and other bone marrow failure syndromes has improved scientific understanding of the ...

. Acquired predisposing factors include:

aplastic anemia Aplastic anemia is a cancer in which the body fails to make blood cells in sufficient numbers. Blood cells are produced in the bone marrow by stem cells that reside there. Aplastic anemia causes a deficiency of all blood cell types: red blood ...

, chemotherapy, prenatal exposure to tobacco, marihuana, and alcohol.

Research directions

Considering the disease is rare, not much research is being done specifically for the AML-M4 subtype. Research regarding the production of granulocyte colony stimulating factor (G-CSF) is being conducted to investigate AMML ability to secrete and synthesize G-CSF. Multiple chemotherapy drugs and its effects are being research in comparison to its treatment success in AML not specifically AML-M4.

References

External links

{{Myeloid malignancy Acute myeloid leukemia