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

• B-ALL with ETV6::RUNX1-like Features
• B-Lymphoblastic Leukemia/Lymphoma with ETV6-RUNX1-like Features

What is B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features? (Definition/Background Information)

• B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features is a subtype of acute lymphoblastic leukemia (ALL), a cancer of the blood and bone marrow that affects the production of white blood cells
• This specific subtype is characterized by genetic alterations involving the fusion of the ETV6 and RUNX1 genes, similar to another subtype known as B-lymphoblastic leukemia/lymphoma with ETV6-RUNX1 fusion. However, the "like features" designation indicates that while the genetic profile resembles ETV6-RUNX1 fusion, there may be additional genetic or clinical characteristics that differentiate it
• This condition primarily affects children but can also occur in adults. The exact cause of B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features is not fully understood, but it is believed to result from a combination of genetic predisposition and environmental factors
• The signs and symptoms of B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features may include fatigue, fever, frequent infections, easy bruising or bleeding, bone pain, swollen lymph nodes, and abdominal discomfort due to an enlarged spleen/liver. The diagnosis typically involves blood tests,  bone marrow biopsy, and genetic testing to identify specific genetic abnormalities
• The complications of B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features can include anemia, bleeding disorders, infections, and organ dysfunction due to infiltration of leukemic cells. Without prompt and effective treatment, the condition can rapidly progress and lead to severe and life-threatening complications
• The treatment options for the condition may include chemotherapy,  targeted therapy, radiation therapy, stem cell transplantation, and supportive care measures to manage symptoms and complications. Treatment choice depends on factors such as the patient's age, overall health, and the extent of the disease
• Given its complex genetic nature, preventive measures for B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features are generally unavailable. However, ongoing research aims to understand the underlying mechanisms better and develop targeted therapies that may improve outcomes for the affected individuals
• Overall outcomes for B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features can vary depending on factors such as the treatment response, the presence of genetic abnormalities, and complications. Many individuals can achieve remission and experience long-term survival with adequate treatment and supportive care. However, close monitoring and follow-up are essential to detect and manage potential recurrences or late effects of treatment

Who gets B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features? (Age and Sex Distribution)

• B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features primarily affects children, although it can also occur in adults
• The peak incidence is observed in children between 2 and 5 years, with a secondary peak in adolescents and young adults. However, cases can occur across a wide age range
• Regarding gender distribution, this subtype of leukemia does not exhibit a significant predilection for either males or females; it affects both genders relatively equally
• Regarding racial or ethnic groups, no substantial evidence suggests a higher prevalence of the condition in any specific racial or ethnic group

However, disparities in access to healthcare and socioeconomic factors may influence the diagnosis and outcomes of individuals from different racial or ethnic backgrounds. Further research is needed to explore potential incidence differences among various population groups.

What are the Risk Factors for B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features? (Predisposing Factors)

The exact causes of B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features are not entirely understood, and the condition often arises sporadically rather than being linked to specific risk factors.

However, several factors may predispose individuals to develop this subtype of leukemia:

• Genetic predisposition: Some individuals may have genetic predispositions or familial syndromes that increase their risk for leukemia. Although rare, certain genetic conditions, such as Down syndrome and Li-Fraumeni syndrome, have been associated with an increased risk of developing leukemia, including B-lymphoblastic leukemia/lymphoma
• Environmental exposures: Exposure to certain environmental factors, such as ionizing radiation, certain chemicals (e.g., benzene), and toxins, may increase the risk of developing leukemia. However, the specific environmental triggers for B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features have not been identified
• Previous cancer treatment: Individuals who have undergone previous cancer treatment, such as chemotherapy or radiation therapy, for other cancers may have an increased risk of developing secondary leukemias, including B-lymphoblastic leukemia/lymphoma. This particularly applies to survivors of childhood cancers treated with intensive chemotherapy and radiation therapy
• Immune system disorders: Certain immune system disorders or conditions that weaken the immune system may increase the risk of developing leukemia. For example, individuals with conditions such as HIV/AIDS or those undergoing immunosuppressive therapy following organ transplantation may be at a higher risk
• Exposure to certain viruses: Although not conclusively proven, some studies suggest a potential link between viral infections, such as Epstein-Barr virus (EBV) and human T-cell lymphotropic virus type 1 (HTLV-1), and the development of leukemia. However, more research is needed to establish a definitive causal relationship

It is important to note that while these factors may increase the risk of developing B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features, not everyone with these predisposing factors will develop the condition. Additionally, many cases of leukemia occur in individuals with no identifiable risk factors, highlighting the complex and multifactorial nature of the disease.

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 B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features? (Etiology)

B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features is primarily caused by genetic alterations involving the fusion of the ETV6 and RUNX1 genes. This fusion gene results from chromosomal translocations, where segments of chromosome 12 (containing the ETV6 gene) and chromosome 21 (containing the RUNX1 gene) break and exchange places, leading to the abnormal fusion of these genes. The resultant ETV6::RUNX1-like fusion gene is a hallmark genetic abnormality observed in this subtype of leukemia.

• The ETV6 gene (also known as the TEL gene) encodes a transcriptional repressor protein involved in normal hematopoiesis, regulating the development and differentiation of blood cells. Similarly, the RUNX1 gene (also known as the AML1 gene) encodes a transcription factor essential for developing blood cells, particularly in forming hematopoietic stem cells and precursor cells
• The fusion of the ETV6 and RUNX1 genes generates an abnormal protein that disrupts normal cellular processes, including cell proliferation, differentiation, and apoptosis (programmed cell death). This ultimately leads to the uncontrolled growth and accumulation of immature lymphoblasts characteristic of leukemia
• While the mechanisms by which the ETV6::RUNX1-like fusion gene contributes to leukemogenesis are not fully understood, it is believed to interfere with normal hematopoietic development by dysregulating gene expression pathways involved in cell growth and differentiation
• In addition to genetic abnormalities, other factors such as environmental exposures, immune system dysfunction, and viral infections may contribute to the development of B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features. However, the primary driver of the disease remains the genetic fusion between ETV6 and RUNX1 genes.

Understanding the underlying molecular mechanisms of this fusion and its impact on cellular processes is crucial for developing targeted therapies and improving outcomes for the affected individuals.

What are the Signs and Symptoms of B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features?

The signs and symptoms of B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features can vary widely among individuals. They may depend on factors such as the extent of the disease, the age of onset, and individual variations in response to leukemia cells.

The common signs and symptoms of this condition include:

• Fatigue and weakness: Persistent feelings of tiredness and weakness, often unrelated to physical activity, can be early indicators of leukemia
• Fever: Recurrent or persistent fevers without an obvious cause may occur due to the body's immune response to leukemia cells
• Frequent infections: Individuals with leukemia may experience frequent infections, such as respiratory infections, urinary tract infections, or skin infections, due to a weakened immune system
• Easy bruising or bleeding: Leukemia can impair the body's ability to produce normal blood cells, leading to easy bruising, bleeding gums, nosebleeds, or prolonged bleeding from minor cuts or injuries
• Bone pain: Leukemia cells can accumulate in the bone marrow, leading to bone pain or tenderness, particularly in the long bones of the arms and legs
• Swollen lymph nodes: Enlarged lymph nodes, especially in the neck, armpits, or groin, may occur due to leukemia cell infiltration
• Abdominal discomfort: Enlargement of the spleen or liver due to infiltration by leukemia cells may cause abdominal pain, fullness, or discomfort

It is important to note that the severity of symptoms can vary widely among individuals. Some individuals may present with mild symptoms that develop gradually over time, while others may experience more severe symptoms or rapid disease progression requiring immediate medical attention.

Additionally, the signs and symptoms of B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features can overlap with other medical conditions, making diagnosis challenging. Early detection and prompt medical evaluation are essential for accurately diagnosing and effectively managing this condition and improving outcomes and quality of life.

How is B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features Diagnosed?

Diagnosing B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features typically involves a combination of clinical evaluation, laboratory tests, imaging studies, and special genetic studies to confirm the diagnosis and assess the extent of the disease.

• Medical history and physical examination: The diagnostic process often begins with a thorough review of the patient's medical history and a comprehensive physical examination. The healthcare provider will inquire about the patient's symptoms, including any recent infections, unexplained fatigue, bruising, bleeding, or other concerning symptoms
• Blood tests: Blood tests play a crucial role in diagnosing leukemia. A complete blood count (CBC) test is typically performed to evaluate various blood cell levels, including red blood cells, white blood cells, and platelets. In leukemia, abnormalities in these blood cell counts, such as leukocytosis (elevated white blood cell count) or anemia (low red blood cell count), may be observed
• Bone marrow aspiration and biopsy: Bone marrow aspiration and biopsy are essential diagnostic procedures for leukemia. During an aspiration, a small sample of bone marrow fluid is extracted from the hipbone or sternum using a needle. A biopsy involves the removal of a small core of bone marrow tissue for further examination. These samples are analyzed under a microscope to assess the presence of abnormal cells and determine leukemia subtypes
• Immunophenotyping: Immunophenotyping, a laboratory technique that uses antibodies to identify specific proteins on the surface of cells, is often performed on bone marrow or blood samples. This helps classify the leukemia cells based on their cell surface markers, providing valuable information for diagnosis and treatment planning
• Cytogenetic analysis: Cytogenetic analysis involves studying the chromosomes of leukemia cells to identify any genetic abnormalities or chromosomal rearrangements, such as the ETV6::RUNX1 fusion gene characteristic of the condition. This analysis helps confirm the diagnosis and may also guide treatment decisions
• Imaging studies: Imaging studies, such as X-rays, ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) scans, may be performed to assess the extent of the disease and identify any complications, such as enlarged lymph nodes or organ involvement
• Lumbar puncture (spinal tap): Sometimes, a lumbar puncture may be performed to collect cerebrospinal fluid from the spinal canal. This procedure helps assess whether leukemia cells have spread to the central nervous system, a potential complication known as central nervous system leukemia

By combining the results of these diagnostic tests, healthcare providers can accurately diagnose B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features and develop a personalized treatment plan tailored to the affected individual’s needs. Early and accurate diagnosis is essential for initiating timely treatment and improving outcomes for affected individuals.

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 B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features?

B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features can lead to various complications. Some may arise due to the underlying disease, while others may result from treatment or disease progression. These complications can significantly impact the patient's quality of life and overall prognosis.

The possible complications associated with this condition include:

• Infections: Leukemia compromises the body's immune system, making individuals more susceptible to infections. Severe or recurrent infections can lead to complications such as sepsis, pneumonia, or meningitis
• Anemia: Leukemia cells can overcrowd the bone marrow, decreasing the production of normal red blood cells. Anemia can cause fatigue, weakness, shortness of breath, and other symptoms of reduced oxygen delivery to tissues
• Bleeding disorders: Leukemia can impair the production of normal platelets, leading to a tendency to bleed excessively or develop spontaneous bruising. Severe thrombocytopenia (low platelet count) can result in life-threatening bleeding episodes
• Organ infiltration: Leukemia cells may infiltrate various organs and tissues, including the spleen, liver, lymph nodes, and central nervous system. Organ infiltration can lead to organ enlargement, dysfunction, and associated symptoms such as abdominal pain, jaundice, or neurological deficits
• Tumor lysis syndrome (TLS): Rapid destruction of leukemia cells during treatment can release large amounts of intracellular contents into the bloodstream, leading to metabolic imbalances such as hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. TLS can cause kidney injury, cardiac arrhythmias, seizures, and other serious complications if not promptly managed
• Central nervous system (CNS) complications: Leukemia cells may spread to the central nervous system, causing symptoms such as headaches, seizures, cranial nerve palsies, and altered mental status. CNS involvement can lead to neurologic deficits and may require aggressive treatment to prevent complications such as leukemic meningitis
• Chemotherapy toxicity: Chemotherapy, the primary treatment modality for leukemia, can cause various side effects and toxicities, including nausea, vomiting, hair loss, bone marrow suppression, neuropathy, and increased susceptibility to infections. Some chemotherapy agents may also have long-term effects on organ function and fertility
• Secondary cancers: Individuals treated for leukemia may be at increased risk of developing secondary cancers later in life due to the mutagenic effects of chemotherapy and radiation therapy. Common secondary malignancies include secondary leukemias, myelodysplastic syndromes, and solid tumors
• Psychosocial and emotional impact: Coping with a diagnosis of leukemia and undergoing intensive treatment can take a significant toll on the patient's mental and emotional well-being. Anxiety, depression, fear of recurrence, and adjustment difficulties are common psychosocial challenges faced by individuals with leukemia and their families
• Treatment-related Complications: Complications related to treatments such as stem cell transplantation, radiation therapy, and immunotherapy may include graft-versus-host disease, radiation-induced tissue damage, cytokine release syndrome, and immune-related adverse events

Overall, the management of B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features requires a comprehensive approach that addresses both the underlying disease and its associated complications. Close monitoring, supportive care measures, and timely intervention are essential for minimizing the risk of complications and improving outcomes for affected individuals.

How is B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features Treated?

The treatment for B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features typically involves a combination of chemotherapy, targeted therapy, radiation therapy, stem cell transplantation, and supportive care measures. The choice of treatment depends on the patient's age, overall health, disease stage, genetic abnormalities, and response to initial therapy.

• Chemotherapy: Chemotherapy is the cornerstone of treatment for B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features
  • It involves using cytotoxic drugs to kill leukemia cells or prevent their growth and division. Chemotherapy regimens typically consist of multiple drugs administered in specific cycles over several weeks or months
  • Common chemotherapy agents include vincristine, prednisone, daunorubicin, cyclophosphamide, and methotrexate. Intensive induction chemotherapy aims to achieve remission by reducing the leukemia cell burden in the bone marrow and peripheral blood
• Targeted therapy:
  • Targeted therapy drugs specifically target molecular pathways or surface antigens involved in the growth and survival of leukemia cells
  • In B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features, targeted therapies may include monoclonal antibodies such as rituximab, which binds to CD20 antigen on B-cells, or tyrosine kinase inhibitors such as dasatinib, which target abnormal signaling pathways implicated in leukemia development
• Radiation therapy: It is often used in combination with chemotherapy for optimal disease control
  • Radiation therapy may be used in specific cases to target localized disease areas, such as bulky lymphadenopathy or central nervous system involvement
  • External beam radiation therapy delivers high-energy radiation to targeted areas, destroying leukemia cells and shrinking tumors
• Stem cell transplantation (SCT): Stem cell transplantation, also known as hematopoietic stem cell transplantation (HSCT), may be considered for eligible patients, particularly those with high-risk or relapsed disease
  • HSCT involves the infusion of healthy stem cells (either from a donor or the patient's cells) into the bloodstream to restore normal blood cell production following high-dose chemotherapy or radiation therapy
  • Allogeneic transplantation using stem cells from a compatible donor offers the potential for long-term disease control but carries risks of graft-versus-host disease and transplant-related complications
• Supportive care measures:
  • These are crucial in managing treatment-related side effects and complications, maintaining the patient's overall well-being, and improving quality of life
  • Supportive care measures may include blood transfusions to correct anemia or thrombocytopenia, antimicrobial therapy to prevent or treat infections, growth factor support to stimulate white blood cell production, pain management, nutritional support, and psychosocial support services for patients and their families

Long-term follow-up measures for patients treated for B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features involve regular medical evaluations, monitoring for late treatment effects, and surveillance for disease recurrence. Depending on the patient's needs and treatment history, follow-up care may include periodic blood tests, imaging studies, cardiac evaluations, thyroid function tests, bone density assessments, and cognitive assessments.

The goal of long-term follow-up is to detect and manage potential late effects of treatment, optimize the patient’s health and quality of life, and provide ongoing support for physical, emotional, and psychosocial well-being.

How can B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features be Prevented?

Currently, no specific preventive measures are known to effectively prevent the development of B-lymphoblastic leukemia/Lymphoma with ETV6::RUNX1-like features. Since the exact causes of this condition are not fully understood and may involve complex genetic and environmental factors, there are no targeted strategies for prevention.

However, several general health recommendations and strategies may help reduce the risk of leukemia and promote overall well-being:

• Healthy lifestyle: Adopting a healthy lifestyle, including maintaining a balanced diet, regular physical activity, adequate sleep, and stress management, can support overall health and immune function
• Avoiding exposure to carcinogens: Minimizing exposure to known carcinogens and environmental toxins, such as tobacco smoke, hazardous chemicals, and ionizing radiation, may help reduce the risk of leukemia and other cancers
• Genetic counseling: Individuals with a family history of leukemia or other cancers may benefit from genetic counseling and testing to assess their risk of inherited genetic predispositions and identify appropriate risk reduction strategies
• Occupational safety: Occupational exposure to chemicals, radiation, or other hazardous substances may increase the risk of leukemia. Following safety protocols and using protective equipment in work environments with potential carcinogenic exposures can help mitigate risks
• Regular health check-ups: Routine medical check-ups and screenings can help detect potential health problems early and facilitate prompt diagnosis and treatment if needed. Maintaining open communication with healthcare providers and discussing any concerns or changes in health is essential for proactive health management

While these measures may contribute to overall health and well-being, it is important to recognize that leukemias often occur sporadically and may not be preventable through lifestyle modifications alone. Research efforts aimed at elucidating the underlying genetic and environmental factors contributing to leukemia development may lead to new insights into prevention strategies in the future.

In the meantime, raising awareness about leukemia, supporting research initiatives, and advocating for improved access to healthcare and early detection methods remain crucial to addressing this disease.

What is the Prognosis of B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features? (Outcomes/Resolutions)

The prognosis of B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features can vary widely depending on factors such as the patient's age, overall health, disease stage, genetic abnormalities, response to treatment, and presence of complications. Timely intervention and appropriate treatment are pivotal in determining the prognosis and outcomes for affected individuals.

• With timely intervention and effective treatment:
  • Achieving remission: Many patients with B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features can achieve complete remission (absence of detectable leukemia cells) with timely intervention and effective treatment, particularly in children and young adults
  • Prolonged disease control: Intensive chemotherapy regimens, targeted therapies, radiation therapy, and stem cell transplantation can help control the disease, prolong survival, and reduce the risk of relapse
  • Improved overall survival: Advances in treatment approaches and supportive care measures have significantly improved survival rates for patients with B-lymphoblastic leukemia/lymphoma. Many patients can achieve long-term remission and live relatively normal lives with appropriate management
• Without timely intervention or inadequate treatment:
  • Disease progression: Without timely intervention or adequate treatment, B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features can progress rapidly, leading to worsening symptoms, complications, and organ dysfunction
  • Increased mortality risk: Untreated or poorly controlled leukemia can lead to life-threatening complications such as infections, bleeding disorders, organ failure, and tumor lysis syndrome, significantly increasing the risk of mortality
  • Reduced quality of life: Disease-related symptoms, treatment-related side effects, and complications can significantly impact the patient's quality of life and functional status, affecting their ability to perform daily activities and participate in social and occupational roles
• Close monitoring, regular follow-up evaluations, and ongoing supportive care are essential components of comprehensive management strategies to achieve long-term disease control and maximize the patient's quality of life
• Achieving complete remission (absence of detectable leukemia cells) after induction chemotherapy is a critical milestone associated with improved long-term outcomes. However, relapse may occur in some cases, necessitating salvage therapies or alternative treatment approaches

Overall, timely diagnosis, appropriate risk stratification, and multidisciplinary treatment planning are crucial for optimizing outcomes and improving the prognosis of patients with B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features. Early intervention and access to specialized cancer care facilities can make a significant difference in the prognosis and survival outcomes of affected individuals.

Additional and Relevant Useful Information for B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features:

• Clinical trials: Participation in clinical trials can provide access to innovative treatment approaches, novel targeted therapies, and investigational drugs for patients with B-Lymphoblastic Leukemia/Lymphoma with ETV6::RUNX1-like Features. Clinical trials also contribute to advancing scientific knowledge and improving treatment outcomes for future patients
• Genetic counseling: Genetic counseling may benefit patients and their families by discussing the implications of genetic testing, inherited predispositions to leukemia, and the risk of recurrence in future generations. Genetic counselors can provide information, support, and guidance regarding genetic testing options, family planning, and cancer risk reduction strategies
• Psychosocial support: Coping with a diagnosis of leukemia can be challenging for patients and their families. Psychosocial support services, including counseling, support groups, educational resources, and holistic therapies, can help address emotional, social, and practical concerns, improve coping strategies, and enhance overall well-being
• Educational resources: Access to reliable and up-to-date educational resources, such as reputable websites, patient advocacy organizations, and informational materials provided by healthcare providers, can empower patients and their families to make informed decisions about treatment options, symptom management, and supportive care measures.
• Long-term survivorship care: Survivors of the condition may require long-term care to monitor for late treatment effects, address ongoing health concerns, and optimize quality of life. Survivorship care plans tailored to the individual's treatment history, risk factors, and follow-up needs can facilitate coordinated care and promote optimal health outcomes
• Advocacy and support networks: Patient advocacy organizations, support networks, and online communities dedicated to leukemia and cancer care can provide valuable peer support, advocacy resources, and opportunities for networking, education, and empowerment for patients, caregivers, and healthcare professionals

Collaboration among patients, caregivers, healthcare providers, researchers, and advocacy organizations is essential for advancing knowledge, improving outcomes, and promoting resilience in the face of leukemia.