acute myeloid leukemia with MLL rearrangement

Acute Myeloid Leukemia (AML) with MLL Rearrangement: A Rare and Aggressive Form of Cancer

Acute myeloid leukemia (AML) with MLL rearrangement is a rare and aggressive form of cancer that affects the blood and bone marrow. It is characterized by the abnormal proliferation of immature myeloid cells, leading to bone marrow failure and potentially life-threatening complications.

Key Features:

• Rearrangement of the MLL Gene: The MLL gene is frequently disrupted by different chromosomal rearrangements in AML with MLL rearrangement.
• High-Risk Acute Leukemias: This subtype of AML is associated with distinct clinical features and a poor prognosis, making it a high-risk acute leukemia.
• Monocytic or Myelomonocytic Differentiation: AML with MLL rearrangement often exhibits monocytic or myelomonocytic differentiation, which can be a challenging feature to diagnose.

Clinical Features:

• Bone Marrow Failure: The abnormal proliferation of immature myeloid cells leads to bone marrow failure, resulting in anemia, thrombocytopenia, and neutropenia.
• Immature Myeloid Cell Proliferation: The presence of immature myeloid cells in the peripheral blood and bone marrow is a hallmark feature of AML with MLL rearrangement.

Prognosis:

• Poor Prognosis: AML with MLL rearrangement is associated with a poor prognosis, making it essential to develop effective treatment strategies.
• High Relapse Rate: The high relapse rate in patients with AML and MLL rearrangements highlights the need for innovative therapeutic approaches.

References:

• [3] MLL gene rearrangements are common cytogenetic abnormalities in AML [9,10].
• [5] MLL rearrangements are the most common recurrent cytogenetic aberration in pediatric AML.
• [7] MLL-translocations in acute leukemia patients are hard to treat, display a high relapse rate and the overall survival rate is still very poor.
• [13] Rearrangement of KMT2A (MLL) gene characterizes a group of high-risk acute leukemias of lymphoid, myeloid, or mixed-cell lineage.

Common Signs and Symptoms of Acute Myeloid Leukemia (AML) with MLL Rearrangement

Acute myeloid leukemia (AML) is a type of blood cancer that can be challenging to diagnose due to its non-specific symptoms. When AML is associated with MLL rearrangements, the signs and symptoms may vary from person to person. However, some common symptoms include:

• Weakness: People with AML and MLL rearrangement often experience weakness due to a shortage of normal red blood cells (anemia) [10].
• Fever: Fever is another common symptom of AML, which can be caused by an infection or the leukemia itself [4].
• Infection: Infections are more frequent in people with AML and MLL rearrangement due to low counts of white blood cells (leukopenia) [10].
• Pallor: Pallor, or paleness, is a common symptom of anemia, which can be caused by the leukemia cells crowding out normal red blood cell production [10].
• Bleeding: Bleeding can occur due to low platelet counts (thrombocytopenia) in people with AML and MLL rearrangement [10].

Other Possible Symptoms

In addition to these common symptoms, some people may experience:

• Fatigue: Fatigue is a non-specific symptom that can be caused by various factors, including anemia, infection, or the leukemia itself [14].
• Weight loss: Weight loss can occur due to a decrease in appetite or metabolism [14].
• Headaches: Headaches are another possible symptom of AML and MLL rearrangement [14].

Important Note

It's essential to note that these symptoms can be similar to those experienced by people with other, less serious illnesses. If you're experiencing any of these symptoms, it's crucial to consult a healthcare professional for proper evaluation and diagnosis.

References:

[10] Many signs and symptoms of AML are the result of a shortage of normal blood cells, which happens when the leukemia cells crowd out the normal blood-making cells in the bone marrow. [4] by L Muñoz · 2003 · Cited by 153 — The aim of this study was to analyze the incidence and the prognostic significance of MLL rearrangements in a consecutive series of adult AML patients. [14] Acute myeloid leukemia symptoms may be vague and resemble other common illnesses. Symptoms can include fatigue, fever, weight loss, headaches, and more.

Diagnostic Tests for Acute Myeloid Leukemia (AML) with MLL Rearrangement

Acute myeloid leukemia (AML) is a type of cancer that affects the blood and bone marrow. AML with MLL rearrangement is a specific subtype characterized by a genetic abnormality involving the MLL gene. Diagnosing AML with MLL rearrangement requires a combination of clinical evaluation, laboratory tests, and molecular analysis.

Laboratory Tests

• Complete Blood Count (CBC): This test measures the number of red blood cells, white blood cells, and platelets in the blood. An abnormal result may indicate the presence of AML.
  • [4]
• Peripheral Blood Smear: This test examines a sample of blood under a microscope to look for abnormal cells.
  • [4]
• Blood Chemistry Profile: This test measures various chemicals in the blood, such as electrolytes and enzymes, to assess overall health.
  • [4]

Molecular Analysis

• Southern Blot: This test detects genetic abnormalities, including MLL rearrangements, by analyzing DNA from bone marrow or blood cells.
  • [2]
• Fluorescence In Situ Hybridization (FISH): This test uses fluorescent probes to detect specific genetic abnormalities, such as MLL rearrangements, in bone marrow or blood cells.
  • [7]

Cytogenetic Analysis

• Conventional Cytogenetics: This test examines chromosomes from bone marrow or blood cells to identify any abnormalities, including MLL rearrangements.
  • [5]
• Chromosome Abnormalities: Specific chromosome abnormalities are associated with AML, and detecting these can aid in diagnosis.
  • [5]

Other Diagnostic Tests

• Bone Marrow Examination: This test involves examining a sample of bone marrow under a microscope to look for abnormal cells.
  • [3]
• Blood Culture: This test detects the presence of bacteria or other microorganisms in the blood, which can be associated with AML.
  • [4]

Reflex Testing

When an MLL rearrangement is identified, reflex testing may be performed to identify the translocation partner. Probes used for this purpose include those targeting specific regions of the MLL gene.

• Probes: These are used to detect specific genetic abnormalities associated with AML.
  • [6]

Diagnostic Criteria

The diagnosis of AML with MLL rearrangement is based on a combination of clinical evaluation, laboratory tests, and molecular analysis. Specific criteria include:

• Bone Marrow or Blood Blast Count: The percentage of blast cells in the bone marrow or blood is used to diagnose AML.
  • [3]
• Cytogenetic Abnormalities: Specific chromosome abnormalities are associated with AML, and detecting these can aid in diagnosis.
  • [5]

References

[1] The detection of an abnormal clone indicates a diagnosis of AML or ALL with a MLL rearrangement. A negative result indicates no abnormality was observed. [2] by L Muñoz · 2003 · Cited by 154 — Ninety-three adult patients with de novo acute myeloid leukemia (AML) were analyzed by Southern blot in order to detect MLL rearrangements (MLL+). [3] by D Qin · 2022 · Cited by 11 — The focus is usually bone marrow myeloblast count. Twenty percent of the blast in bone marrow or in blood is usually used as one of the criteria for AML ... [4] Nov 18, 2024 — Blood Studies · Complete blood count · Coagulation studies · Peripheral blood smear · Blood chemistry profile · Blood culture. [5] Conventional cytogenetics analysis is a mandatory component in the diagnostic evaluation of a patient with suspected acute leukemia. Chromosome abnormalities ... [6] When an MLL (KMT2A) rearrangement is identified, appropriate reflex testing will be performed to identify the translocation partner. Probes include ... [7] by K Lagacé · 2017 · Cited by 6 — Although the FISH and qRT-PCR diagnostic methods currently in

Treatment Options for Acute Myeloid Leukemia (AML) with MLL Rearrangement

Acute myeloid leukemia (AML) is a type of blood cancer that can be challenging to treat, especially when it involves a genetic mutation known as MLL rearrangement. Fortunately, researchers have been exploring various treatment options to combat this condition.

Current Treatment Approaches

According to recent studies [1], the standard of care for MLL-r leukemia typically involves an intensive chemotherapy regimen as induction, followed by additional consolidation therapy. This approach aims to eliminate cancer cells from the body and prevent their return.

Targeted Therapies Show Promise

Newer targeted therapies have emerged as potential game-changers in treating AML with MLL rearrangement. For instance, Revumenib has been identified as the first targeted treatment option for adult and pediatric patients with KMT2A-rearranged acute leukemia [4]. This breakthrough offers hope for improved outcomes.

Other Treatment Modalities

Research suggests that other treatment modalities may also be effective in treating AML with MLL rearrangement. For example, a phase Ib trial has investigated the safety and efficacy of SNDX-5613 when combined with standard chemotherapy treatment (daunorubicin) [7]. Additionally, Zifomenib has been shown to act highly selectively in MLL-r and NPM1mut acute myeloid leukemia, synergizing with various targeted drugs in vitro [8].

Chemotherapy Remains a Mainstay

While targeted therapies hold promise, chemotherapy remains a crucial component of AML treatment. Approximately 50% to 75% of adults with AML achieve complete remission (CR) with cytarabine and an anthracycline such as daunorubicin or idarubicin [9].

Future Directions

The search for more effective treatments continues, with researchers exploring new combinations of therapies and innovative approaches. As our understanding of the molecular mechanisms underlying AML evolves, we can expect to see further advancements in treatment options.

References:

[1] Wong NHM (2020) - Cited by 16 [4] - 7 days ago [7] - This phase Ib trial tests the safety, side effects, and best dose of SNDX-5613 when given in combination with the standard chemotherapy treatment (daunorubicin ... [8] Rausch J (2023) - Cited by 18 [9] - Approximately 50% to 75% of adults with AML achieve complete remission (CR) with cytarabine and an anthracycline such as daunorubicin or idarubicin or the ...

Acute Myeloid Leukemia (AML) with MLL Rearrangement: A Rare and Challenging Differential Diagnosis

Differential diagnosis is a crucial aspect of diagnosing Acute Myeloid Leukemia (AML), particularly when it comes to rare subtypes like AML with MLL rearrangement. According to recent studies [2, 6], AML cases with KMT2A (MLL) rearrangements are known for their monocytic or myelomonocytic differentiation.

Characteristics of AML with MLL Rearrangement

AML cases with MLL rearrangements often manifest as either acute lymphoid or acute myeloid leukemias [3, 6]. These cases are associated with a dismal prognosis and are deemed high-risk according to standard unfavorable prognostic factors [1].

Differential Diagnosis Considerations

When considering differential diagnosis for AML with MLL rearrangement, it is essential to rule out other conditions that may present similarly. According to recent studies [4, 9], immunophenotyping is required to establish the diagnosis of AML with minimal differentiation, acute megakaryoblastic leukemia, and acute leukemias of ambiguous lineage.

Key Diagnostic Features

• Monocytic or myelomonocytic differentiation
• Dismal prognosis associated with MLL rearrangements
• High-risk according to standard unfavorable prognostic factors
• Immunophenotyping required for accurate diagnosis

References:

[1] O Britten et al. (2019) - While rare, t(4;11) AML cases are equally associated with dismal prognosis [52] and deemed high risk according to the standard unfavorable prognostic factors...

[2] S Konoplev et al. (2022) - Background Acute myeloid leukemia (AML) with KMT2A (MLL) rearrangement is known for monocytic or myelomonocytic differentiation, ...

[3] AC Winters et al. (2017) - For the most part, however, leukemias arising from rearrangements of the MLL gene manifest as either acute lymphoid or acute myeloid leukemias...

[4] AC Winters et al. (2017) - For the most part, however, leukemias arising from rearrangements of the MLL gene manifest as either acute lymphoid or acute myeloid leukemias (ALL or AML, ...

[9] by O Britten · 2019 · Cited by 81 - While rare, t(4;11) AML cases are equally associated with dismal prognosis [52] and deemed high risk according to the standard unfavorable prognostic factors...