Acute Promyelocytic Leukemia: Causes, Symptoms And Treatments

Causes Of Acute Promyelocytic Leukemia

Acute promyelocytic leukemia is a type of acute myeloid leukemia, a type of cancer of white blood cells. During the development of acute promyelocytic leukemia, immature granulocytes, also known as promyelocytes, accumulate abnormally in the blood. In this type of cancer, there is a chromosomal translocation involving the alpha gene of the retinoic acid receptor (Jimenez et al., 2020). This distinguishes acute promyelocytic leukemia from other forms of acute myeloid leukemia and other responses to retinoic acid therapy.

Acute promyelocytic leukemia has been observed to account for approximately 12% of all cases of acute myeloid leukemia. Median age is expected to be approximately 30–40 years, considerably younger than other myeloid leukemia subtypes, which are usually around 70 years (Yilmaz, Kantarjian, Ravandi, 2021). Incidence of this cancer is higher in people in Latin America and southern Europe. Due to the carcinogenic effects of these agents, carcinogenicity is also observed in patients treated with topoisomerase II inhibitors as secondary malignancies. Patients with breast cancer account for the majority of acute promyelocytic leukemia. Approximately 40% of patients with this disease apparently carry chromosomal abnormalities such as trisomy 8 and her chromosome 17, which have no long-term consequences (Stahl & Tallman, 2019).

Figure: Auer rods in acute promyelocytic leukemia (Jimenez et al., 2020)

The efficacy of acute promyelocytic leukemia is superior to that of other types of leukemia. However, the onset of cancer is relatively acute compared to other types of cancer, and mortality is significantly higher in the early stages. If the disease is left untreated, median survival is less than 1 month (Jimenez et al., 2020). However, in recent years, advances in treatment have transformed the disease from a highly fatal disease to a highly curable one. Patients experience massive hemorrhage, often intracranial hemorrhage, which is presumed to be the leading cause of death in the population. In countries with inadequate access to healthcare, 10% of reported cases result in premature death from hemorrhage. In relatively developing countries, patient mortality rises to around 25-30% (Yilmaz, Kantarjian, Ravandi, 2021). Risk factors associated with premature death from hammer are delayed disease diagnosis, elevated white blood cell counts on admission, and delayed initiation of treatment.

Acute promyelocytic leukemia is characterized by the presence of the retinoic acid receptor alpha gene on chromosome 17, which is involved in a reciprocal translocation of the promyelocytic leukemia gene on chromosome 15 (Kayser, Schlenk & Platzbecker, 2018). Several other gene arrangements have been observed in acute promyelocytic leukemia, with the retinoic acid receptor alpha gene being a promyelocytic leukemia zinc finger, nuclear matrix-associated gene, signal converter and transcriptional activator. 5B, the regulatory subunit 1 alpha of the protein. Kinase A, and many others. Fusion of the promyelocytic leukemia gene with the retinoic acid receptor alpha gene results in the expression of a hybrid protein with multiple altered functions (Kayser, Schlenk & Platzbecker, 2018). Auer rods are found in the blood of patients with acute promyelocytic leukemia.

Symptoms Of Acute Promyelocytic Leukemia

Abnormalities observed in acute promyelocytic leukemia are normal anemia, neutropenia, thrombocytopenia, increased prothrombin time, increased partial thromboplastin time, and decreased fibrinogen. These conditions are different from the usual conditions of acute promyelocytic leukemia. Differential diagnosis of acute promyelocytic leukemia is different types of hematologic malignancies, acute lymphoblastic leukemia, chronic myelogenous leukemia, acute myelogenous leukemia and chronic lymphocytic leukemia (Yilmaz, Kantarjian & Ravandi, 2021) . Although each disease mentioned has different causes and treatments, acute promyelocytic leukemia can be diagnosed separately as this disease.
Diagnostics that help identify acute promyelocytic leukemia are microscopic examination of blood smears or biopsy of bone marrow or bone marrow aspirate. However, identifying the retinoic acid receptor alpha gene/promyelocytic leukemia gene by polymerase chain reaction would be diagnostic of disease development (Jimenez et al., 2020).

There are several treatment options for acute promyelocytic leukemia, which have proven effective in most cases. Of these, all-trans retinoic acid therapy and ATRA therapy have been shown to be effective. ATRA therapy supports dissociation of the NCOR-HDACL complex from the RAR, which allows DNA transcription and differentiation, allowing immature granulocytes to form mature granulocytes (Stahl & Tallman, 2019). ). This treatment has a unique side effect called differentiation syndrome. Alternative treatments include monoclonal antibody therapy, which has been shown to be effective in treating acute promyelocytic leukemia.

Fetal and neonatal hemolytic disease, also known as fetal erythroblastosis, is an alloimmune disorder that develops in the fetus at birth. It is formed when her IgG molecules produced by the mother are transferred across the placenta to the fetus. Some of the antibodies that pass through attack antigens on fetal red blood cells in the fetal circulation, destroying and destroying those cells. As a result, reticulocytosis and anemia can develop in the fetus. The severity of this condition varies from mild to severe and can ultimately lead to fetal death due to heart failure (Nassar & Wehbe, 2018). In moderate and severe erythroblastosis fetalis, the fetal blood contains excessive amounts of immature erythroblasts.

Antibodies are normally produced to fight foreign antigens when the body is exposed to them. When a pregnant mother is exposed to such foreign antigens, the mother’s immune system produces her IgG antibodies against the foreign antigen. When these antibodies reach the fetus across the placenta, they attack the fetal red blood cells, causing fetomaternal hemorrhage. Blood transfusions, blood group incompatibility, and bleeding are three commonly observed factors that sensitize pregnant mothers to foreign antigens (Heerema-McKenney, 2022).

Figure: Haemolytic disease of the foetus and new born (Nassar & Wehbe, 2018)

Fetal maternal bleeding occurs during the transfer of fetal blood cells across the placenta and can occur during childbirth, abortion, termination of pregnancy, and ectopic pregnancy. It was observed that in most cases, pregnant women had received blood transfusions, probably due to therapeutic intervention (Vossoughi & Spitalnik, 2019). Although blood group and Rh system identification is performed prior to the transfusion process, in some cases the blood group may not match the stated status due to inadvertence. Another reason for the occurrence of blood group incompatibility is observed when maternal and paternal blood types are incompatible with each other (Patil et al., 2021). As a result, the fetus may have the characteristics of the father’s blood type, with incompatibility between the mother’s blood type and the blood type. As a result, the mother’s immune system produces antibodies against antigens present in the fetal blood, causing agglutination. This may be due to hemolytic disease of the newborn.

Treatment Of Acute Promyelocytic Leukemia

There are several ways to prevent hemolytic disease in newborns. This includes immunoglobulin therapy to prevent maternal sensitization reactions. However, this is only possible with his Rho immunoglobulin, not other types of blood group incompatibility. Early in pregnancy, maternal titers rise and, if there was previous loss, intravenous immunoglobulin, also known as IVIG or aggressive antibodies. Plasmapheresis in early pregnancy can reduce maternal titers by displacing and removing plasma antibodies (Agarwal et al., 2019). Both of these treatments can be performed on women with a history of both hydrops fetalis and fetal loss.

Intrauterine blood transfusion can be done either intraperitoneally or intravenously. In most cases, physicians prefer intravenous transfusion to intraperitoneal transfusion, and it is performed up to 36 weeks of gestation (Nassar & Wehbe, 2018). Steroid administration is another method prescribed to pregnant women before intrauterine transfusion and during preterm labor to help the fetus’ lungs mature. Phenobarbital has actually been administered to pregnant women and may aid fetal liver maturation and reduce the risk of hyperbilirubinemia (Vossoughi & Spitalnik, 2019). If it is suspected that the fetus may develop hemolytic disease, emergency labor with induction of labor should be performed to prevent the development of the disease. Babies born with erythroblastosis fetalis should be monitored for approximately 3–5 months to detect signs of developing anemia (Nassar & Wehbe, 2018). Babies may need blood transfusions after birth. Proper antenatal and postnatal care of the baby may prevent erythroblastosis fetalis and avoid long-term complications (Heerema-McKenney, 2022). Treatment for this condition includes blood transfusions to prevent anemia in the baby and immunotherapy to reduce the risk of red blood cell destruction. It also helps reduce bilirubin circulating in the blood.

There are several ways to prevent hemolytic disease in newborns. This includes immunoglobulin therapy to prevent maternal sensitization reactions. However, this is only possible with his Rho immunoglobulin, not other types of blood group incompatibility. Early in pregnancy, maternal titers rise and, if there was previous loss, intravenous immunoglobulin, also known as IVIG or aggressive antibodies. Plasmapheresis in early pregnancy can reduce maternal titers by displacing and removing plasma antibodies (Agarwal et al., 2019). Both of these treatments can be performed on women with a history of both hydrops fetalis and fetal loss.

Intrauterine blood transfusion can be done either intraperitoneally or intravenously. In most cases, physicians prefer intravenous transfusion to intraperitoneal transfusion, and it is performed up to 36 weeks of gestation (Nassar & Wehbe, 2018). Steroid administration is another method prescribed to pregnant women before intrauterine transfusion and during preterm labor to help the fetus’ lungs mature. Phenobarbital has actually been administered to pregnant women and may aid fetal liver maturation and reduce the risk of hyperbilirubinemia (Vossoughi & Spitalnik, 2019). If it is suspected that the fetus may develop hemolytic disease, emergency labor with induction of labor should be performed to prevent the development of the disease. Babies born with erythroblastosis fetalis should be monitored for approximately 3–5 months to detect signs of developing anemia (Nassar & Wehbe, 2018). Babies may need blood transfusions after birth. Proper antenatal and postnatal care of the baby may prevent erythroblastosis fetalis and avoid long-term complications (Heerema-McKenney, 2022). Treatment for this condition includes blood transfusions to prevent anemia in the baby and immunotherapy to reduce the risk of red blood cell destruction. It also helps reduce bilirubin circulating in the blood.

References

Agarwal, P. K., Rahi, S., Baberwal, M. C., & Mishra, H. K. (2019). A Case Report of Hydrops Fetalis with Cystic Hygroma. jp-journals-10057-0107 (archive.org)

Heerema-McKenney, A. (2022). Erythroblastosis Fetalis, Hydrops Fetalis, and Transplacental Hemorrhage. Benirschke’s Pathology of the Human Placenta, 633-667. Erythroblastosis Fetalis, Hydrops Fetalis, and Transplacental Hemorrhage | SpringerLink

Jimenez, J. J., Chale, R. S., Abad, A. C., & Schally, A. V. (2020). Acute promyelocytic leukemia (APL): a review of the literature. Oncotarget, 11(11), 992. https://dx.doi.org/10.18632%2Foncotarget.27513

Kayser, S., Schlenk, R. F., & Platzbecker, U. (2018). Management of patients with acute promyelocytic leukemia. Leukemia, 32(6), 1277-1294. Management of patients with acute promyelocytic leukemia | Leukemia (nature.com)

Nassar, G. N., & Wehbe, C. (2018). Erythroblastosis Fetalis. Erythroblastosis Fetalis – Abstract – Europe PMC

Patil, A., Brocato, B., Uhlmann, R. A., & Mari, G. (2021). Erythroblastosis fetalis. In Clinical Maternal-Fetal Medicine Online (pp. 53-1). CRC Press. Erythroblastosis fetalis | Avinash Patil, Brian Brocato, Rebecca A. Uh (taylorfrancis.com)

Stahl, M., & Tallman, M. S. (2019). Acute promyelocytic leukemia (APL): remaining challenges towards a cure for all. Leukemia & lymphoma, 60(13), 3107-3115. https://doi.org/10.1080/10428194.2019.1613540

Stahl, M., & Tallman, M. S. (2019). Differentiation syndrome in acute promyelocytic leukaemia. British journal of haematology, 187(2), 157-162. https://doi.org/10.1111/bjh.16151

Vossoughi, S., & Spitalnik, S. L. (2019). Conquering erythroblastosis fetalis: 50 years of RhIG. Transfusion, 59(7), 2195-2196. https://doi.org/10.1111/trf.15307

Yilmaz, M., Kantarjian, H., & Ravandi, F. (2021). Acute promyelocytic leukemia current treatment algorithms. Blood cancer journal, 11(6), 1-9. Acute promyelocytic leukemia current treatment algorithms | Blood Cancer Journal (nature.com)