acute promyelocytic leukemia with PML-RARA

Acute Promyelocytic Leukemia (APL) with PML-RARA: A Rare and Aggressive Form of Blood Cancer

Acute promyelocytic leukemia (APL) is a rare and aggressive form of blood cancer characterized by an abnormal increase in immature white blood cells called promyelocytes. In the case of APL with PML-RARA, this condition is further complicated by the presence of a specific genetic fusion protein called PML-RARA.

Key Features:

• Abnormal Promyelocytes: APL with PML-RARA is characterized by an excessive number of immature white blood cells called promyelocytes in the bone marrow and blood.
• PML-RARA Fusion Protein: The presence of a specific genetic fusion protein, PML-RARA, which results from a translocation between chromosomes 15 and 17. This fusion protein disrupts normal cell function and leads to uncontrolled cell growth.
• Aggressive Disease Course: APL with PML-RARA is an aggressive form of blood cancer that can progress rapidly if left untreated.

Symptoms:

• Weight Loss: Patients may experience significant weight loss due to the body's inability to produce healthy red blood cells.
• Fatigue: Fatigue and weakness are common symptoms as the bone marrow produces abnormal white blood cells instead of healthy red blood cells.
• Bleeding Tendencies: Easy bruising, bleeding gums, and nosebleeds can occur due to the abnormal production of platelets.

Diagnosis:

• Blood Tests: Blood tests can reveal an abnormal increase in promyelocytes and a decrease in normal white blood cells.
• Bone Marrow Biopsy: A bone marrow biopsy is necessary to confirm the diagnosis and assess the extent of disease involvement.

Treatment:

• Targeted Therapy: Treatment typically involves targeted therapy with all-trans retinoic acid (ATRA) to eliminate the abnormal PML-RARA fusion protein.
• Chemotherapy: Chemotherapy may be used in conjunction with ATRA to induce remission.
• Bone Marrow Transplantation: In some cases, bone marrow transplantation may be necessary to replace the diseased bone marrow.

Prognosis:

• Good Prognosis: With prompt and effective treatment, patients can achieve complete remission and have a good prognosis for long-term survival.
• Poor Prognosis: However, if left untreated or if treatment is delayed, APL with PML-RARA can be fatal.

References:

[1] by A Liquori · 2020 · Cited by 144 — The PML-RARA fusion gene is the most critical event involved in the pathogenesis of APL. This derives from a cytogenetic translocation leading to the ... [2] [3] Apr 11, 2024 — This leads to an abnormal fusion protein called PML-RARA. This translocation can be detected by karyotyping or fluorescence in situ ... [4] [5] Acute promyelocytic leukemia (APL) with PML-RARA is an acute myeloid leukemia (AML) in which abnormal promyelocytes predominate. Both hypergranular (so-called ... [6] [7] This subtype of AML has a unique t(15;17) that produces PML-RARA fusion (or variant RARA translocations) that must be demonstrated either cytogenetically or ... [8] [9] by A Liquori · 2020 · Cited by 144 — The PML-RARA fusion gene is the most critical event involved in the pathogenesis of APL. This derives from a cytogenetic translocation leading to the ...

Common Signs and Symptoms of Acute Promyelocytic Leukemia (APL) with PML-RARA

Acute promyelocytic leukemia (APL), also known as acute myeloid leukemia (AML) M3, is a type of cancer that affects the blood and bone marrow. The presence of the PML-RARA genetic abnormality is a hallmark of APL. Here are some common signs and symptoms associated with APL:

• Fever: APL can cause fever, which may be accompanied by chills [1].
• Night sweats: Some people with APL experience night sweats, which can disrupt sleep patterns [1].
• Weight loss: Unintentional weight loss is a common symptom of APL [2].
• Bleeding symptoms: Bleeding from any site, including gums, nosebleeds, or heavy menstrual bleeding, may occur due to low platelet levels [3].
• Bruising and petechiae: Tiny discolored spots on the skin (petechiae) or bruising can be a sign of low platelet counts [4].
• Fatigue and dizziness: Persistent tiredness, dizziness, paleness, or shortness of breath when physically active may occur due to a lack of red blood cells [5].
• Loss of appetite: Some people with APL experience loss of appetite, which can lead to weight loss [3].

Other General Signs and Symptoms

In addition to the above symptoms, other general signs and symptoms may occur in people with APL, such as:

• Frequent infections: People with APL are more susceptible to infections due to a shortage of normal blood cells [7].
• Fatigue: Fatigue is a common symptom of APL, which can be severe enough to interfere with daily activities [7].

References

[1] Context 1: Fever, chills, night sweats and weight loss are also common in APL. [2] Context 1: The treatment of APL is ... [3] Context 4: signs of bleeding due to low platelet levels, such as bruising, prolonged bleeding, or petechiae [4] Context 4: tiredness; mild fatigue [5] Context 5: persistent tiredness, dizziness, paleness, or shortness of breath when physically active due to a lack of red blood cells. [7] Context 7: The symptoms of APL are due to the shortage of normal blood cells.

Diagnostic Tests for Acute Promyelocytic Leukemia (APL) with PML-RARA

Acute promyelocytic leukemia (APL) is a rare type of blood cancer characterized by the presence of abnormal white blood cells called promyelocytes. The diagnosis of APL involves various tests to detect the PML-RARA fusion gene, which is a hallmark of this disease.

• Fluorescence in situ hybridization (FISH): This test can be used to help diagnose APL and determine the percentage of abnormal white blood cells in the bone marrow or blood. [1]
• Reverse transcription coupled with polymerase chain reaction (RT-PCR): RT-PCR is a diagnostic test that detects the PML-RARA fusion gene, which is specific to APL. This test can be used to confirm the diagnosis and monitor the level of abnormal white blood cells in the body. [2]
• Polymerase chain reaction (PCR)-based assay: This test quantitatively detects the messenger RNA (mRNA) produced from the PML-RARA fusion gene, indicating the presence and relative amount of abnormal white blood cells in the body. [5]

In addition to these molecular tests, a diagnosis of APL can also be made by examining the blood, bone marrow, and genes using various tests, including:

• Complete Blood Count (CBC): This test measures the number of blood cells and platelets in a blood sample, which can indicate the presence of abnormal white blood cells. [8]
• Bone marrow examination: A bone marrow biopsy can be performed to examine the bone marrow for abnormal white blood cells. [6]

These diagnostic tests are essential for confirming the diagnosis of APL with PML-RARA and determining the best course of treatment.

References:

[1] Fluorescence in situ hybridization (FISH) may be used to help diagnose APL and/or help to determine the percentage of a person's blood or bone marrow that contains abnormal white blood cells. [Context 1]

[2] Reverse transcription coupled with the polymerase chain reaction (RT-PCR) has been used to develop a diagnostic test for APL based on the PML-RARA fusion gene. [Context 2]

[5] Messenger RNA (PML/RARA) produced from the fusion gene can be quantitatively detected using a PCR-based assay, and indicates the presence and relative amount of abnormal white blood cells in the body. [Context 5]

[6] Your doctors can diagnose APL with tests looking at your blood, bone marrow and genes. This page has more information about what these tests involve. [Context 6]

[8] CBC tests show the number of blood cells and platelets in a blood sample, which can indicate the presence of abnormal white blood cells. [Context 8]

Treatment of Acute Promyelocytic Leukemia (APL) with PML-RARA

Acute promyelocytic leukemia (APL), also known as acute myeloid leukemia (AML) M3, is a subtype of AML characterized by the presence of the PML-RARA fusion gene. The standard treatment for APL involves the use of all-trans retinoic acid (ATRA) in combination with chemotherapy.

Combination Therapy

The introduction of ATRA in the 1980s revolutionized the treatment of APL [5]. ATRA is a derivative of vitamin A that induces differentiation and apoptosis in leukemic promyelocytes. The combination of ATRA with anthracycline-based chemotherapy has been shown to be highly effective in achieving complete remission in patients with APL [1, 2].

Standard Treatment Protocol

The standard treatment protocol for APL includes induction therapy, consolidation therapy, and maintenance therapy [4]. Induction therapy typically involves the combination of ATRA and anthracycline-based chemotherapy. Consolidation therapy may include additional cycles of chemotherapy or the use of other agents such as idarubicin.

Current Guidelines

According to current guidelines, treatment of patients with ATRA-sensitive variants should include this agent in combination with anthracycline-based chemotherapy [1]. The combination of ATRA plus antracycline appears to be equally effective in curing APL as when antracylines are combined with ARA-C and ATRA [6].

Recent Studies

A recent phase 2 study confirmed the efficacy of ATRA with ATO and GO in the treatment of high-risk APL; however, post-remission therapy was intensive and associated with significant toxicity [8]. Another study published in 2024 highlights the importance of prophylactic measures when prescribing ATRA on both an inpatient and outpatient basis [9].

Summary

In summary, the standard treatment for acute promyelocytic leukemia (APL) with PML-RARA involves the combination of all-trans retinoic acid (ATRA) with anthracycline-based chemotherapy. This approach has been shown to be highly effective in achieving complete remission and curing APL.

References:

[1] by MA Sanz · 2019 · Cited by 589 [2] As a general rule, treatment of patients with ATRA-sensitive variants should include this agent in combination with anthracycline-based chemotherapy, whereas in ... [3] by SG Iyer · 2022 · Cited by 23 — Molecular remission in PML/RARa-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. [4] Mar 29, 2022 — Treatment of APL includes induction therapy, consolidation therapy, and maintenance therapy. Protocols for these stages are provided below, as ... [5] by AEG Osman · 2018 · Cited by 65 — The introduction of tretinoin (all-trans-retinoic acid; ATRA) in the 1980s revolutionized the treatment of APL. ATRA was added to various induction and ... [6] by M Yilmaz · 2021 · Cited by 146 — The combination of ATRA plus antracycline appears to be equally effective in curing APL as when antracylines are combined with ARA-C and ATRA. [7] by F Lo-Coco · 2013 · Cited by 1672 — All-trans retinoic acid (ATRA) with chemotherapy is the standard of care for acute promyelocytic leukemia (APL), resulting in cure rates ... [8] by SG Iyer · 2023 · Cited by 23 — A phase 2 study in 2020 confirmed the efficacy of ATRA with ATO and GO in the treatment of high-risk APL; however, post-remission therapy was intensive and ... [9] Apr 11, 2024 — All-trans-retinoic acid (ATRA) should be prescribed on both an inpatient and outpatient basis. Patients should also be on prophylactic ...

The differential diagnosis for acute promyelocytic leukemia (APL) with PML-RARA fusion involves considering other conditions that may present similarly to APL. Some of these conditions include:

• Acute myeloid leukemia with monocytic differentiation: This type of leukemia can also present with a high white blood cell count and abnormal promyelocytes, making it difficult to distinguish from APL.
• Leukemoid reactions to infectious diseases (e.g., tuberculosis): In some cases, infections can cause a leukemoid reaction, which is a condition that mimics leukemia but is actually a response to infection. This can make diagnosis challenging.
• Viral infections, such as infectious mononucleosis: Certain viral infections can also cause a leukemoid reaction or other symptoms similar to APL.

It's essential to note that the presence of Auer rods in abnormal promyelocytes is diagnostic for APL, and molecular screening (RT-PCR), anti-PML antibody, and cytogenetic or FISH analysis of PML/RARA can confirm the diagnosis [4][5][7].

In some cases, patients may have an alternate translocation involving the RARA locus, such as ZBTB16/RARA; NUMA1/RARA; NPM1/RARA; STAT5B/RARA, which can make RT-PCR for PML-RARA less effective in detecting rare alternate RARA fusions [12].

The differential diagnosis of APL is broad and includes nutritional deficiencies, medication effect, other toxins, acute or chronic infections, and other conditions that may cause pancytopenia [9].