Acute Myeloid Leukemia
Disease Details
Family Health Simplified
- Description
- Acute myeloid leukemia (AML) is an aggressive type of cancer that originates in the bone marrow and results in the rapid accumulation of abnormal white blood cells, which interfere with normal blood production.
- Type
- Acute myeloid leukemia (AML) is a type of cancer that affects the blood and bone marrow. It is not typically inherited and usually arises from acquired genetic mutations. Most cases of AML are sporadic, meaning they occur in individuals without a family history of the disease. However, certain genetic syndromes and familial predispositions can increase the risk of developing AML.
- Signs And Symptoms
- Most signs and symptoms of AML are caused by the crowding out in bone marrow of space for normal blood cells to develop. A lack of normal white blood cell production makes people more susceptible to infections. A low red blood cell count (anemia) can cause fatigue, paleness, shortness of breath and palpitations. A lack of platelets can lead to easy bruising, bleeding from the nose (epistaxis), small blood vessels on the skin (petechiae) or gums, or bleeding with minor trauma. Other symptoms may include fever, fatigue worse than what can be attributed to anaemia alone, weight loss and loss of appetite.Enlargement of the spleen may occur in AML, but it is typically mild and asymptomatic. Lymph node swelling is rare in most types of AML, except for acute myelomonocytic leukemia (AMML). The skin can be involved in the form of leukemia cutis; Sweet's syndrome; or non-specific findings: flat lesions (macules), raised lesion papules, pyoderma gangrenosum and vasculitis.Some people with AML may experience swelling of the gums because of infiltration of leukemic cells into the gum tissue. Involvement of other parts of the body such as the gastrointestinal tract, respiratory tract and other parts is possible but less common. One area which has particular importance for treatment is whether there is involvement of the meninges around the central nervous system.
- Prognosis
- Multiple factors influence prognosis in AML, including the presence of specific mutations, and a person with AML's age. In the United States between 2011 and 2016, the median survival of a person with AML was 8.5 months, with the 5 year survival being 24%. This declines with age, with the poorer prognosis being associated with an age greater than 65 years, and the poorest prognosis seen in those aged 75–84.As of 2001, cure rates in clinical trials have ranged from 20 to 45%; although clinical trials often include only younger people and those able to tolerate aggressive therapies. The overall cure rate for all people with AML (including the elderly and those unable to tolerate aggressive therapy) is likely lower. Cure rates for APL can be as high as 98%.
- Onset
- Acute Myeloid Leukemia (AML) typically has a sudden onset. Symptoms can appear quickly and might include fatigue, fever, frequent infections, easy bruising or bleeding, weight loss, and pain in bones or joints. It requires prompt medical attention for diagnosis and treatment.
- Prevalence
- Acute myeloid leukemia (AML) primarily affects adults, with an incidence rate of about 4.3 per 100,000 people annually in the United States. The disease is less common in children, making up about 1% of pediatric cancers. Globally, AML represents approximately 0.5% of all new cancer cases each year.
- Epidemiology
- AML is a relatively rare cancer. There were 19,950 new cases in the United States in 2016. In 2018, AML accounted for 1.2% of all cancer deaths in the United States.The incidence of AML increases with age and varies between countries. The median age when AML is diagnosed ranges between 63 and 71 years in the UK, Canada, Australia and Sweden, compared with 40 to 45 years in India, Brazil and Algeria.AML accounts for about 90% of all acute leukemias in adults, but is rare in children. The rate of therapy-related AML (AML caused by previous chemotherapy) is expected to rise with an increase in the use of chemotherapy, an ageing population and more patients surviving their initial chemotherapy treatment; therapy-related disease accounts for just under 10% of all cases of AML. AML is slightly more common in men, with a male-to-female ratio of 1.3:1 to 1.4:1. Incidence is also seen to differ by ethnicity, with caucasians having higher recorded incidences and the lowest recorded incidences being in Pacific Islanders and native Alaskans.In the UK, AML accounts for 31% of all leukemia cases, and around 3,100 people were diagnosed with the disease each year in 2016–2018.
- Intractability
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Acute myeloid leukemia (AML) is a serious and aggressive form of cancer that impacts the blood and bone marrow. While the disease can be challenging to treat, it is not necessarily intractable. Treatment outcomes can vary depending on several factors including the patient's age, overall health, specific genetic mutations present, and how well the disease responds to initial therapy.
Common treatments include chemotherapy, targeted therapy, and in some cases, stem cell transplants. Advances in medical research continue to improve treatment protocols and outcomes, offering hope to many patients. However, relapse and resistance to treatment can occur, making the management of AML complex and requiring ongoing medical assessment and intervention. - Disease Severity
- Disease severity for acute myeloid leukemia (AML) can vary significantly depending on various factors, including the patient's age, overall health, genetic mutations of the leukemia cells, and the specific subtype of AML. Generally, AML is considered a rapidly progressing and potentially life-threatening disease that requires prompt and aggressive treatment. The prognosis and treatment outcomes can vary, with some patients achieving remission while others may experience recurrent disease.
- Healthcare Professionals
- Disease Ontology ID - DOID:9119
- Pathophysiology
- The malignant cell in AML is the myeloblast. In normal development of blood cells (hematopoiesis), the myeloblast is an immature precursor of myeloid white blood cells; a normal myeloblast will mature into a white blood cell such as an eosinophil, basophil, neutrophil or monocyte. In AML, though, a single myeloblast accumulates genetic changes which stop maturation, increase its proliferation, and protect it from programmed cell death (apoptosis). Much of the diversity and heterogeneity of AML is because leukemic transformation can occur at a number of different steps along the differentiation pathway. Genetic abnormalities or the stage at which differentiation was halted form part of modern classification systems.Specific cytogenetic abnormalities can be found in many people with AML; the types of chromosomal abnormalities often have prognostic significance. The chromosomal translocations encode abnormal fusion proteins, usually transcription factors whose altered properties may cause the "differentiation arrest". For example, in APL, the t(15;17) translocation produces a PML-RARA fusion protein which binds to the retinoic acid receptor element in the promoters of several myeloid-specific genes and inhibits myeloid differentiation.The clinical signs and symptoms of AML result from the growth of leukemic clone cells, which tends to interfere with the development of normal blood cells in the bone marrow. This leads to neutropenia, anemia, and thrombocytopenia. Other symptoms can arise from the infiltration of malignant cells into parts of the body, such as the gingiva and skin.Many cells develop mutations in genes that affect epigenetics, such as DNA methylation. When these mutations occur, it is likely in the early stages of AML. Such mutations include in the DNA demethylase TET2 and the metabolic enzymes IDH1 and IDH2, which lead to the generation of a novel oncometabolite, D-2-hydroxyglutarate, which inhibits the activity of epigenetic enzymes such as TET2. Epigenetic mutations may lead to the silencing of tumor suppressor genes and/or the activation of proto-oncogenes.
- Carrier Status
- Acute myeloid leukemia (AML) does not have a carrier status. It is not a hereditary disease that can be carried and passed down in a typical Mendelian fashion. Instead, AML is a type of cancer that typically arises from acquired genetic mutations in the myeloid cells found in the bone marrow. These mutations can be influenced by various risk factors, including exposure to certain chemicals, radiation, and prior chemotherapy, among others.
- Mechanism
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Acute myeloid leukemia (AML) is a heterogeneous group of cancers 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. Here’s a brief overview of its mechanism and molecular mechanisms:
**Mechanism:**
AML primarily involves the uncontrolled proliferation of myeloid precursors, which are immature cells in the bone marrow. These cells fail to differentiate into mature blood cells and instead accumulate, leading to a decrease in the number of functional white blood cells, red blood cells, and platelets. This results in symptoms like anemia, infections, and bleeding disorders due to the marrow's impaired ability to produce normal blood cells.
**Molecular Mechanisms:**
1. **Genetic Mutations:** AML is driven by various genetic mutations that result in the disruption of normal cell differentiation and proliferation processes. Common mutations involve genes such as FLT3, NPM1, DNMT3A, IDH1/2, and RUNX1.
- **FLT3 Mutations:** The FLT3 gene encodes a receptor tyrosine kinase. Mutations, particularly internal tandem duplications (FLT3-ITD) or tyrosine kinase domain (TKD) mutations, lead to constitutive activation of the receptor, promoting uncontrolled cell division and survival.
- **NPM1 Mutations:** Mutations in the NPM1 gene lead to the aberrant localization of the nucleophosmin protein in the cytoplasm rather than the nucleus, disrupting normal cell function and contributing to leukemogenesis.
- **IDH1 and IDH2 Mutations:** These mutations alter the enzyme activity of isocitrate dehydrogenase, leading to the production of an oncometabolite (2-hydroxyglutarate) that disrupts normal cellular differentiation.
2. **Chromosomal Abnormalities:** Structural alterations such as translocations, deletions, and inversions can also play a critical role in AML. For example:
- **t(8;21)(q22;q22) and inv(16)(p13;q22):** These chromosomal rearrangements create fusion genes (e.g., RUNX1-RUNX1T1 and CBFB-MYH11) that interfere with normal hematopoietic differentiation programs.
3. **Epigenetic Changes:** Alterations in DNA methylation, histone modification, and chromatin remodeling are also significant in AML pathogenesis. These changes can silence tumor suppressor genes or activate oncogenes without altering the DNA sequence directly.
- **DNMT3A Mutations:** DNMT3A is involved in DNA methylation, a process critical for gene expression regulation. Mutations in DNMT3A can lead to widespread changes in the methylation landscape, contributing to leukemogenesis.
4. **Signaling Pathways:** Dysregulation of various signaling pathways, including the RAS/MAPK, PI3K/AKT, and JAK/STAT pathways, supports the survival and proliferation of leukemic cells.
Overall, AML is a complex disease arising from a combination of genetic, epigenetic, and molecular abnormalities that disrupt the normal maturation and function of blood cells. - Treatment
- First-line treatment of AML consists primarily of chemotherapy, and is divided into two phases: induction and consolidation. The goal of induction therapy is to achieve a complete remission by reducing the number of leukemic cells to an undetectable level; the goal of consolidation therapy is to eliminate any residual undetectable disease and achieve a cure. Hematopoietic stem cell transplantation is usually considered if induction chemotherapy fails or after a person relapses, although transplantation is also sometimes used as front-line therapy for people with high-risk disease. Efforts to use tyrosine kinase inhibitors in AML continue.
- Compassionate Use Treatment
-
Acute Myeloid Leukemia (AML) can be challenging to treat, especially in cases where conventional treatments fail. Compassionate use, off-label, and experimental treatments may provide hope in these scenarios:
1. **Compassionate Use Treatments**:
- These involve accessing investigational drugs not yet approved by regulatory agencies but showing promise in clinical trials. This is typically done when no other treatment options are available.
- Examples include certain targeted therapies and immunotherapies in late-stage trials.
2. **Off-Label Treatments**:
- Off-label use involves prescribing an FDA-approved drug for an indication, dose, or patient population not included in the approved labeling.
- Examples include:
- **Venetoclax**: Approved for chronic lymphocytic leukemia, used off-label for AML, particularly in combination with hypomethylating agents like azacitidine or decitabine.
- **Sorafenib**: Approved for kidney and liver cancer, sometimes used off-label for FLT3-mutated AML.
3. **Experimental Treatments**:
- These are treatments still under investigation in clinical trials but not yet approved for general use.
- Examples include:
- **FLT3 Inhibitors**: Gilteritinib and quizartinib are under investigation for FLT3-mutated AML.
- **CPX-351 (Vyxeos)**: A liposomal formulation of cytarabine and daunorubicin, under research for secondary and high-risk AML.
- **IDH1/2 Inhibitors**: Ivosidenib for IDH1 mutations and enasidenib for IDH2 mutations.
- **CAR-T Cell Therapy**: Being tested for its applicability to AML.
Participation in clinical trials may offer access to these cutting-edge therapies, under careful medical supervision. - Lifestyle Recommendations
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For acute myeloid leukemia (AML), lifestyle recommendations can support overall health and complement medical treatments. Key considerations include:
1. **Nutrition:** Maintain a balanced diet rich in fruits, vegetables, whole grains, and lean proteins. Proper nutrition can boost the immune system and help the body recover from treatments.
2. **Hydration:** Drink plenty of fluids to stay hydrated, especially during chemotherapy.
3. **Exercise:** Engage in regular, moderate physical activity as tolerated to improve stamina and reduce fatigue. Consult a healthcare provider before starting any exercise regimen.
4. **Rest:** Prioritize adequate sleep and rest to help the body heal and manage treatment side effects.
5. **Avoid Infections:** Practice good hygiene, avoid large crowds, and stay away from people who are sick to minimize infection risk, especially during periods of low white blood cell counts.
6. **Avoid Smoking and Alcohol:** Avoid tobacco and limit alcohol consumption, as these can impair the immune system and overall recovery.
7. **Regular Medical Follow-Up:** Keep all medical appointments and follow the treatment plan prescribed by healthcare providers.
8. **Stress Management:** Employ stress-reducing techniques such as meditation, yoga, or counseling to help cope with the emotional challenges of AML.
These lifestyle adjustments can aid in managing symptoms and improving quality of life during treatment for AML. Always consult healthcare professionals before making any significant lifestyle changes. - Medication
- Olutasidenib (Rezlidhia) was approved for medical use in the United States in December 2022.
- Repurposable Drugs
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There are several existing drugs that are being explored for repurposing in the treatment of acute myeloid leukemia (AML). Some of these include:
1. **Venetoclax** - Originally approved for chronic lymphocytic leukemia, it's being studied for use in AML in combination with other agents.
2. **Arsenic Trioxide** - Used for acute promyelocytic leukemia, research is ongoing for its potential use in AML.
3. **Auranofin** - An anti-rheumatic agent that has shown potential in preclinical studies for AML.
4. **Thalidomide** and its derivatives - Known for treating multiple myeloma, they are under investigation for their efficacy in AML.
5. **Metformin** - Commonly used for type 2 diabetes, it has shown some promise in preclinical studies for AML due to its effects on cellular metabolism.
These drugs are part of ongoing research and clinical trials focused on finding more effective treatments for acute myeloid leukemia. - Metabolites
-
Acute myeloid leukemia (AML) is a type of cancer that originates in the blood and bone marrow and is characterized by an overproduction of immature white blood cells, known as myeloblasts. Due to the rapid proliferation of these cells, there are specific metabolites and biomolecular alterations that could be associated with the disease. Key metabolites and changes often include:
1. **2-Hydroxyglutarate (2-HG):** Elevated levels, especially in cases with IDH1 or IDH2 mutations.
2. **Lactate:** Increased levels due to the enhanced glycolytic activity (Warburg effect) in leukemic cells.
3. **Succinate and Fumarate:** May be elevated due to disruptions in the tricarboxylic acid (TCA) cycle.
4. **Amino Acids:** Aberrant levels of amino acids such as glycine, glutamine, and asparagine can be observed, reflecting altered metabolic needs of proliferating cells.
5. **Nucleotides:** Increased nucleotide synthesis to support rapid cell proliferation.
These metabolic changes can provide insights into disease state, progression, and potential therapeutic targets. - Nutraceuticals
- There is limited evidence to support the effective use of nutraceuticals in the treatment of acute myeloid leukemia (AML). Nutraceuticals, such as vitamins, minerals, and herbal supplements, may provide general health benefits but should not replace conventional treatments like chemotherapy, targeted therapy, or hematopoietic stem cell transplantation. It's essential for patients to consult with their healthcare providers before using any nutraceuticals to ensure they do not interfere with standard treatments.
- Peptides
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Acute myeloid leukemia (AML) is a type of cancer that affects the blood and bone marrow. Regarding treatments and research involving peptides and nanoparticles (nan):
1. **Peptides**: In AML, peptides can be used for various therapeutic purposes. They can act as signaling molecules, aid in the development of peptide-based vaccines, or serve as targeting agents to deliver drugs specifically to leukemia cells. Peptide-based immunotherapies are being investigated to enhance the body’s immune response against AML cells.
2. **Nanoparticles (Nan)**: Nanoparticles are being explored for their potential to improve AML treatment by enhancing drug delivery and minimizing side effects. They can be engineered to carry chemotherapy drugs directly to the cancer cells, reducing the impact on healthy cells. Additionally, nanoparticles can be designed to target specific leukemia cell markers, leading to more precise and effective treatments.
Both peptides and nanoparticles offer promising avenues for advancing AML treatment and improving patient outcomes through more targeted and efficient therapies.