What are the other Names for this Condition? (Also known as/Synonyms)

• Acute Myeloid Leukemia with t(8;21)(q22;q22)
• AML with RUNX1::RUNX1T1 Fusion
• RUNX1-RUNX1T1-Positive Acute Myeloid Leukemia

What is Acute Myeloid Leukemia with RUNX1::RUNX1T1 Fusion? (Definition/Background Information)

• Acute Myeloid Leukemia (AML) with RUNX1::RUNX1T1 Fusion is a subtype of AML characterized by a specific genetic abnormality involving the fusion of two genes: RUNX1 and RUNX1T1. This fusion gene arises due to a chromosomal translocation t(8;21)(q22;q22), where a portion of chromosome 8 containing the RUNX1 gene fuses with a region on chromosome 21 containing the RUNX1T1 gene
• RUNX1 and RUNX1T1 are both transcription factors that play crucial roles in normal hematopoiesis, the process by which blood cells are produced in the body. The fusion of these genes leads to the production of an abnormal protein that disrupts normal blood cell development, resulting in the proliferation of immature and dysfunctional myeloid cells characteristic of acute myeloid leukemia
• Individuals with Acute Myeloid Leukemia with RUNX1::RUNX1T1 Fusion typically present with symptoms similar to other subtypes of AML, including fatigue, weakness, fever, easy bruising or bleeding, and frequent infections. Complications may arise due to bone marrow failure, such as anemia, thrombocytopenia, and neutropenia, increasing the risk of bleeding and infections
• Diagnosis of AML with RUNX1::RUNX1T1 Fusion involves bone marrow aspiration, biopsy, and cytogenetic and molecular genetic testing to identify the characteristic chromosomal translocation. The treatment usually involves induction chemotherapy to achieve remission, followed by consolidation therapy, which may include additional chemotherapy or stem cell transplantation. Targeted therapies and novel treatment approaches may also be considered based on the specific genetic features of the disease
• The prognosis for those with Acute Myeloid Leukemia with RUNX1::RUNX1T1 Fusion varies depending on several factors, including age, overall health, genetic profile, and response to treatment. Some patients achieve long-term remission, while others may experience disease relapse or require ongoing management to control the disease. Close monitoring and personalized treatment strategies are crucial for optimizing outcomes in individuals with AML with RUNX1::RUNX1T1 Fusion

Who gets Acute Myeloid Leukemia with RUNX1::RUNX1T1 Fusion ? (Age and Sex Distribution)

• Acute Myeloid Leukemia (AML) with RUNX1::RUNX1T1 Fusion can occur in individuals of all ages, but it is most commonly diagnosed in adults
• The median age at diagnosis is around 40 to 50 years old. However, pediatric cases of this subtype of AML have also been reported, albeit less frequently
• Compared to females, males have a slight predilection to develop AML with RUNX1::RUNX1T1 Fusion
• Worldwide, individuals across all racial and ethnic groups are prone to this malignancy

What are the Risk Factors Acute Myeloid Leukemia with RUNX1::RUNX1T1 Fusion? (Predisposing Factors)

The risk factors for Acute Myeloid Leukemia (AML) with RUNX1::RUNX1T1 Fusion may include the following:

Genetic predisposition:

• Inherited genetic mutations or predispositions may increase the risk of developing AML with RUNX1::RUNX1T1 Fusion
• Individuals with genetic syndromes such as Down syndrome (trisomy 21) have an elevated risk of developing this subtype of AML

Previous cancer treatment: Exposure to certain chemotherapy agents or radiation therapy for previous cancers may increase the risk of developing secondary AML, including cases with RUNX1::RUNX1T1 Fusion.

Environmental and lifestyle factors: Exposure to carcinogenic substances such as benzene or tobacco smoke may contribute to the development of AML. However, their specific role in this subtype is not well defined.

Age and gender:

• Advanced age is a general risk factor for AML, including RUNX1::RUNX1T1 Fusion subtype. The risk of AML increases with age, with most cases diagnosed in adults
• Studies have shown that this AML subtype occurs more frequently in males than females, although the exact reasons for this difference are not fully understood

Occupational exposures:

• Some occupations, such as those involving chemicals or heavy metals exposure, may pose a higher risk of developing AML
• Workers in agriculture, manufacturing, and petroleum refining industries may be at increased risk

Immune system disorders:

• Certain autoimmune diseases or conditions that affect the immune system may predispose individuals to AML, although the mechanisms are not fully understood
• Disorders such as aplastic anemia or myelodysplastic syndromes (MDS) may increase the risk of developing AML, including the RUNX1::RUNX1T1 Fusion subtype

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one's chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of   Acute Myeloid Leukemia with RUNX1::RUNX1T1 Fusion? (Etiology)

Acute Myeloid Leukemia with RUNX1::RUNX1T1 Fusion may be caused by the following factors:

Chromosomal translocation:

• The primary cause of Acute Myeloid Leukemia (AML) with RUNX1::RUNX1T1 Fusion is a specific chromosomal translocation known as t(8;21)(q22;q22)
• This translocation involves a piece of chromosome 8 (q22) containing the RUNX1 ((also known as AML1)) gene and a portion of chromosome 21 (q22) containing the RUNX1T1 (also known as ETO) gene
• The translocation results in the fusion of these genes, producing a chimeric protein that disrupts normal hematopoiesis and promotes leukemogenesis

Genetic mutations:

• Besides the chromosomal translocation, additional genetic mutations may contribute to the development of AML with RUNX1::RUNX1T1 Fusion
• Mutations in other genes involved in hematopoiesis or leukemogenesis, such as FLT3, NPM1, or CEBPA, may occur concurrently and further drive the progression of the disease

Environmental exposures:

• While the exact environmental triggers for AML with RUNX1::RUNX1T1 Fusion are not fully understood, exposure to certain environmental factors such as benzene or ionizing radiation has been implicated in increasing the risk of developing AML
• These exposures may act as secondary factors that promote leukemic transformation in individuals with underlying genetic abnormalities

Inherited predisposition:

• In some cases, inherited genetic predispositions or syndromes may increase the susceptibility to developing AML, including the subtype with RUNX1::RUNX1T1 fusion
• For instance, individuals with Down syndrome (trisomy 21) have a higher risk of developing AML, often of the RUNX1::RUNX1T1 fusion subtype, due to genetic factors

Immune system dysregulation:

• Dysfunctions in the immune system or immune-related disorders may also play a role in the development of AML
• Conditions that lead to immune suppression or dysregulation, such as autoimmune diseases or certain immunodeficiency disorders, could potentially contribute to leukemic transformation in susceptible individuals

AML with RUNX1::RUNX1T1 Fusion is categorized as a subtype of Core Binding Factor (CBF) AML, which also includes AML with CBFB-MYH11 Fusion (inv(16)(p13q22)/t(16;16)(p13;q22)). This subtype is associated with distinct clinical and biological features, including a relatively favorable prognosis compared to other subtypes of AML.

What are the Signs and Symptoms of Acute Myeloid Leukemia with RUNX1::RUNX1T1 Fusion?

The signs and symptoms of Acute Myeloid Leukemia with RUNX1::RUNX1T1 Fusion may vary from one individual to another and include:

General symptoms:

• Fatigue and weakness due to decreased red blood cell production (anemia)
• Easy bruising and bleeding resulting from low platelet counts (thrombocytopenia)
• Increased susceptibility to infections due to reduced white blood cell counts (neutropenia)

Specific symptoms:

• Bone pain or tenderness: Often in the long bones or pelvis due to leukemia cell infiltration
• Enlarged liver or spleen (hepatosplenomegaly): Caused by the accumulation of leukemia cells in these organs
• Weight loss: Unintentional weight loss may occur due to the disease
• Fever and night sweats: Common symptoms related to infections or the body's response to leukemia cells

Neurological symptoms:

• Headaches: Can occur due to increased intracranial pressure or leukemic infiltration of the central nervous system
• Visual disturbances: Rarely, leukemia cells may infiltrate the eyes, causing visual changes or blurred vision

Respiratory symptoms: Shortness of breath resulting from anemia or, in some cases, leukemic infiltration of the lungs.

Gastrointestinal symptoms:

• Abdominal pain or discomfort: This may be due to hepatosplenomegaly or gastrointestinal involvement by leukemia cells
• Nausea and vomiting: It can occur as a result of disease or side effects of treatment

Skin changes:

• Petechiae or ecchymosis: Small red or purple spots on the skin caused by bleeding under the skin
• Paleness or jaundice: Pale skin or yellowing of the skin and eyes due to anemia or liver involvement

Other symptoms:

• Swollen lymph nodes (lymphadenopathy) sometimes occur, especially if the leukemia cells infiltrate lymph nodes
• Joint pain or swelling: This can occur due to leukemic infiltration of joints or as a nonspecific disease symptom

How is Acute Myeloid Leukemia with RUNX1::RUNX1T1 Fusion Diagnosed?

The diagnosis of  Acute Myeloid Leukemia (AML) with RUNX1::RUNX1T1 Fusion may involve a combination of the following tests and exams:

Initial evaluation: medical history and physical examination

• The healthcare provider will review the patient's medical history, including any symptoms and previous health conditions
• A thorough physical examination will help assess for signs such as enlarged lymph nodes, hepatosplenomegaly, or abnormal skin findings

Laboratory tests:

• Complete blood count (CBC) with differential:
  • This blood test measures the levels of red blood cells, white blood cells, and platelets
  • AML often presents with low red blood cells (anemia), low white blood cells (neutropenia), and low platelets (thrombocytopenia)
• Peripheral blood smear: A sample of the patient's blood is examined under a microscope for abnormal or immature blood cells, common in AML

Bone marrow aspiration and biopsy:

• A procedure where a sample of bone marrow is extracted from the hipbone or breastbone and examined under a microscope
• This helps confirm the diagnosis of AML and assess the percentage of blast cells (immature white blood cells) present

Genetic and molecular testing:

• Cytogenetic analysis: Examines the chromosomes of leukemia cells to identify specific genetic abnormalities, such as the t(8;21)(q22;q22) translocation characteristic of AML with RUNX1::RUNX1T1 Fusion
• Fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR): These molecular tests can detect the presence of specific fusion genes, such as RUNX1::RUNX1T1, which confirms the subtype of AML

Additional tests:

• Flow cytometry: Analyzes the proteins on the surface of leukemia cells to determine their immunophenotype, aiding in diagnosis and classification
• Lumbar puncture (spinal tap): If there are neurological symptoms or suspicion of central nervous system involvement, a lumbar puncture may be performed to collect cerebrospinal fluid for analysis

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Acute Myeloid Leukemia with RUNX1::RUNX1T1 Fusion?

The possible Complications of Acute Myeloid Leukemia with RUNX1::RUNX1T1 Fusion include:

Infections:

• Leukemia compromises the immune system, leading to an increased risk of infections
• Infections can range from mild respiratory infections to severe bloodstream infections (sepsis), which can be life-threatening

Bleeding and clotting disorders:

• Low platelet counts (thrombocytopenia) can result in easy bruising, bleeding gums, and prolonged bleeding from minor cuts or injuries
• In some cases, abnormal clotting (disseminated intravascular coagulation) can occur, leading to excessive clot formation and organ damage

Anemia-related complications:

• Decreased red blood cell production (anemia) can cause fatigue, weakness, shortness of breath, and pale skin
• Severe anemia may necessitate blood transfusions or other supportive treatments

Organ Infiltration:

• Leukemia cells can infiltrate various organs, such as the liver, spleen, lymph nodes, and central nervous system
• Organ infiltration may lead to hepatosplenomegaly (enlarged liver and spleen), lymphadenopathy (swollen lymph nodes), and neurological symptoms if the central nervous system is involved

Tumor lysis syndrome (TLS):

• Rapid breakdown of leukemia cells during treatment can release large amounts of cellular contents into the bloodstream
• This can overwhelm the body's ability to process these substances, leading to electrolyte imbalances, kidney damage, and cardiac complications

Secondary cancers: Some treatments for AML, such as chemotherapy and radiation therapy, can increase the risk of developing secondary cancers later in life.

Psychological and emotional impact: Coping with a diagnosis of AML and undergoing intensive treatments can lead to emotional distress, anxiety, depression, and post-traumatic stress disorder (PTSD) in some patients.

Treatment-related complications: Chemotherapy and stem cell transplantation, while essential for treating AML, can cause a range of side effects and complications, including nausea, vomiting, hair loss, infertility, and graft-versus-host disease (in the case of transplantation).

Long-term effects: Survivors of AML may experience long-term effects such as cognitive impairments, cardiovascular complications, and hormonal imbalances due to the disease and its treatments. Regular monitoring and supportive care are essential to manage these potential complications.

How is Acute Myeloid Leukemia with RUNX1::RUNX1T1 Fusion Treated?

Acute Myeloid Leukemia (AML) with RUNX1::RUNX1T1 Fusion is typically treated with a combination of chemotherapy, targeted therapy, and sometimes stem cell transplantation. The specific treatment approach may vary based on factors such as the patient's age, overall health, genetic profile of the leukemia cells, and response to initial therapy.

Chemotherapy:

• Induction therapy: The initial phase of treatment aims to achieve remission by using intensive chemotherapy regimens that target leukemia cells
• Consolidation therapy: After achieving remission, consolidation therapy may be administered to eliminate any remaining leukemia cells further and reduce the risk of relapse
• Chemotherapy drugs: Commonly used chemotherapy drugs for AML include cytarabine (Ara-C) and anthracyclines such as daunorubicin or idarubicin

Targeted therapy:

• Tyrosine kinase inhibitors (TKIs): TKIs such as midostaurin or gilteritinib may be used in combination with chemotherapy for AML cases with specific genetic mutations, including FLT3-ITD mutations that may co-occur with RUNX1::RUNX1T1 fusion
• Targeted therapies are designed to interfere with specific molecules or pathways involved in leukemia cell growth and survival

Stem cell transplantation:

• Allogeneic stem cell transplant: In some cases, particularly for younger patients or those with high-risk diseases, allogeneic stem cell transplantation may be considered after achieving remission
• This procedure involves replacing the patient's diseased bone marrow with healthy stem cells from a compatible donor (usually a sibling or unrelated matched donor)

Supportive care:

• Supportive care measures are essential throughout the treatment process to manage side effects and complications of therapy
• This may include blood transfusions to address anemia or low platelet counts, antibiotics to prevent or treat infections, and medications to alleviate nausea, pain, or other symptoms

Clinical trials:

• Participation in clinical trials may be recommended, especially for patients with relapsed or refractory disease or those with specific genetic profiles that may benefit from investigational treatments
• Clinical trials help evaluate new therapies, treatment combinations, and targeted agents to improve outcomes for AML patients

Monitoring and follow-up:

• After completing treatment, patients require regular monitoring and follow-up visits to assess their response to therapy, detect any signs of relapse, and manage the long-term effects of treatment
• Monitoring may include blood tests, bone marrow evaluations, imaging studies, and other assessments based on individual needs

Supportive care and symptom management: Supportive care measures, including blood transfusions, growth factors (e.g., G-CSF), antimicrobial prophylaxis, and management of treatment-related side effects (e.g., nausea, mucositis), play a crucial role in improving patient outcomes and quality of life.

Patients with AML must receive care from a multidisciplinary team of healthcare professionals, including hematologists, oncologists, nurses, and supportive care specialists, to ensure comprehensive and personalized treatment plans.

How can Acute Myeloid Leukemia with RUNX1::RUNX1T1 Fusion be Prevented?

It may not be possible to prevent the development of Acute Myeloid Leukemia (AML) with RUNX1::RUNX1T1 Fusion. However, the following measures may be considered to lower the risk of its development:

• Avoiding exposure to carcinogens: Limiting exposure to known carcinogens such as benzene, ionizing radiation, and certain chemicals used in manufacturing, agriculture, and petroleum refining may lower the risk of developing leukemia
• Healthy lifestyle choices: Adopting a healthy lifestyle can contribute to overall well-being and potentially reduce the risk of developing certain cancers, including leukemia. This includes maintaining a balanced diet, regular exercise, avoiding tobacco use, and limiting alcohol consumption
• Occupational safety measures: Individuals working in occupations with potential exposure to carcinogens should follow safety protocols, use protective equipment, and undergo regular health screenings to monitor for any early signs of illness
• Genetic counseling: Genetic counseling and testing may be beneficial for individuals with a family history of genetic syndromes or inherited conditions associated with an increased risk of leukemia. This can help assess the risk and provide guidance on potential preventive measures or early detection strategies
• Early detection and monitoring: While it may not prevent AML, early detection through routine medical check-ups, blood tests, and health screenings can lead to prompt diagnosis and treatment, which may improve outcomes and reduce complications

After completing initial treatment, long-term follow-up and survivorship care are essential for monitoring for late effects, managing potential complications (e.g., secondary cancers, cardiac toxicity), and addressing psychosocial needs. Survivorship programs may include regular health screenings, lifestyle counseling, fertility preservation options, and support services for patients and caregivers.

What is the Prognosis of Acute Myeloid Leukemia with RUNX1::RUNX1T1 Fusion? (Outcomes/Resolutions)

The Prognosis of Acute Myeloid Leukemia (AML) with RUNX1::RUNX1T1 Fusion depends upon the signs and symptoms and associated complications, if any.

Favorable prognosis:

• AML with RUNX1::RUNX1T1 Fusion is generally associated with a favorable prognosis compared to other AML subtypes
• Patients with this subtype of AML often respond well to initial treatment, achieving remission more frequently than some other genetic subtypes

Remission rates: The remission rate for AML with RUNX1::RUNX1T1 Fusion can be relatively high, with a significant percentage of patients achieving complete remission (CR) after induction chemotherapy.

Relapse rates:

• While initial response rates are favorable, there is still a risk of relapse after achieving remission
• The risk of relapse varies depending on factors such as the patient's age, genetic profile, response to initial treatment, and presence of additional genetic mutations

Certain prognostic factors can influence the outcomes of AML with RUNX1::RUNX1T1 Fusion, including:

• Genetic mutations: The co-occurrence of specific genetic mutations, such as FLT3-ITD, NPM1, or CEBPA mutations, can impact prognosis
• Age: Younger patients often have better outcomes than older adults

Response to treatment: Achieving complete remission and minimal residual disease (MRD) negativity after treatment is associated with improved outcomes.

Treatment advances: Advances in treatment approaches, including targeted therapies such as tyrosine kinase inhibitors (TKIs) and allogeneic stem cell transplantation, have improved outcomes for patients with AML, including those with specific genetic subtypes like RUNX1::RUNX1T1 fusion.

Survival rates:

• Overall, the 5-year survival rate for AML with RUNX1::RUNX1T1 Fusion is relatively favorable compared to other AML subtypes
• However, it is important to note that individual outcomes can vary widely, and close monitoring, timely interventions, and personalized treatment plans are crucial for optimizing prognosis and long-term survival

Relapse and salvage therapy:

• In cases where relapse occurs, salvage therapies such as alternative chemotherapy regimens, targeted therapies, or stem cell transplantation may be considered to achieve remission again
• The success of salvage therapy depends on various factors, including the patient's overall health, response to previous treatments, and genetic characteristics of the leukemia cells

Additional and Relevant Useful Information for Acute Myeloid Leukemia with RUNX1::RUNX1T1 Fusion:

Risk stratification and treatment decisions:

• AML with RUNX1::RUNX1T1 Fusion is often classified as a favorable-risk subtype based on cytogenetic and molecular analyses
• Risk stratification helps guide treatment decisions, with low-risk patients typically receiving standard chemotherapy regimens and high-risk patients undergoing additional therapies such as stem cell transplantation

Minimal residual disease (MRD) monitoring:

• Monitoring for minimal residual disease, which refers to small amounts of leukemia cells after treatment, is crucial for assessing treatment response and predicting relapse risk
• Techniques such as flow cytometry, polymerase chain reaction (PCR), and next-generation sequencing (NGS) are used to detect MRD and guide treatment decisions

Genetic mutations and targeted therapies:

• In addition to the RUNX1::RUNX1T1 fusion, AML cells may harbor other genetic mutations that influence prognosis and treatment response
• Targeted therapies, such as FLT3 inhibitors (e.g., midostaurin, gilteritinib) for FLT3-ITD mutations or IDH inhibitors (e.g., ivosidenib, enasidenib) for IDH mutations, may be used in combination with chemotherapy or as maintenance therapy

Role of allogeneic stem cell transplantation:

• Allogeneic stem cell transplantation (SCT) is considered a potentially curative option for eligible patients, particularly those with high-risk disease features or relapsed/refractory AML
• SCT involves replacing the patient's diseased bone marrow with stem cells from a compatible donor, aiming to eradicate leukemia cells and restore normal blood cell production