Causes of Acute Promyelocytic Leukemia
Acute promyelocytic leukaemia is a type of acute myeloid leukemia which is a type of cancer of white blood cells. During the development of acute promyelocytic leukemia, accumulation of the immature granulocytes which are also termed as promyelocytes occurs in the blood abnormally. Have this type of cancer is featured by translocation of the chromosome which involves retinoic acid receptor alpha gene (Jimenez et al., 2020). This distinguishes acute promyelocytic leukemia from other type of acute myeloid leukemia along with the responsiveness to other retinoic acid therapy.
The acute promyelocytic leukemia is observed to represent about 12% of the total acute myeloid leukemia cases. The average age is observed to be around 30 to 40 years that is considerably younger as compared with the other subtypes of the accused myeloid leukemia which is usually observed to be 70 years (Yilmaz, Kantarjian & Ravandi, 2021). The incident rate of this type of cancer is higher in the population of the Latin America and South European origin population. It is also observed in patient as secondary malignancy who have been receiving treatment with the topoisomerase II inhibitors because of the carcinogenic effect of the agents. Patient suffering from breast cancer also represents the majority of the acute promyelocytic leukemia. It is evident that about 40% of the patient who has been suffering from the disorder have chromosomal abnormality including trisomy 8 and isochromosome 17, although it does not have long term results (Stahl & Tallman, 2019).
Figure: Auer rods in acute promyelocytic leukemia (Jimenez et al., 2020)
The effect of acute promyelocytic leukemia is better as compared to other type of leukemia. However due to acuteness of the onset of the cancer is relatively higher than other types death in the initial stage is significantly more. If the condition is left untreated, median survival is observed to be less than one month (Jimenez et al., 2020). However, in the recent years it was transformed from highly fatal disease too highly curable disease by the advancement of the treatment process. The patient experience severe bleeding which is often observed to be intracranial hemorrhage is estimated to be the leading cause of death in the population. Death at the initial stage due to hemorrhage is observed among 10% of the reported cases in the countries Jose sing adequate access to the healthcare facility. The rates of death are increased to about 25 to 30% among the patient in comparatively less developed countries (Yilmaz, Kantarjian & Ravandi, 2021). The risk factors that are associated with the early death pause by the hammer is r delayed diagnosis of the condition, elevated count of the white blood cells during admission and late initiation of the treatment.
Acute promyelocytic leukemia is characterised by the presence of retinoic acid receptor alpha gene on the chromosome 17 which is involved in reciprocal translocation sweets promyelocytic leukemia gene on the chromosome 15 (Kayser, Schlenk & Platzbecker, 2018). Several other gene arrangements have been observed in case of acute promyelocytic leukemia fusing the retinoic acid receptor alpha gene to the promyelocytic leukemia zinc finger, nuclear matrix associated gene, signal transducer and activator of transcription 5B, protein kinase A regulatory subunit 1 alpha and many more. The fusion between the promyelocytic leukemia gene and the retinoic acid receptor alpha gene results in the expression of hybrid protein that has several altered functions (Kayser, Schlenk & Platzbecker, 2018). Auer rods are observed in the blood of patient with acute promyelocytic leukemia.
Symptoms of Acute Promyelocytic Leukemia
The abnormalities that are observed during acute promyelocytic leukemia are normal anemia, neutropenia, thrombocytopenia, elevated prothrombin time, elevated partial thromboplastin time and low fibrinogen. These conditions differ acute promyelocytic leukemia from normal state. The differential diagnosis in case of acute promyelocytic leukemia are different types of hematologic malignancies, acute lymphoblastic leukemia chronic myeloid leukemia acute myeloid leukemia and chronic lymphocytic leukemia (Yilmaz, Kantarjian & Ravandi, 2021). Although each of the mentioned conditions have different causes of occurrence and therapies however, acute promyelocytic leukemia can be differentially diagnosed as this stated condition.
The diagnosis that would help to establish acute promyelocytic leukemia is microscopy examination of blood films or biopsy of bone marrow or bone marrow aspirate. However, polymerase chain reaction for identifying the retinoic acid receptor alpha gene/ promyelocytic leukemia gene would help to diagnose the occurrence of the disease (Jimenez et al., 2020).
There are several treatments for the acute promyelocytic leukemia which have been found to be effective in most of the cases. Among these the all trans retinoic acid or ATRA therapy have been found to be effective. The ATRA therapy helps the dissociation of the NCOR-HDACL complex from the RAR allowing the transcription and differentiation of the DNA to form mature granulocytes from immature ones (Stahl & Tallman, 2019). This therapy is associated with unique side effect of the differentiation syndrome. Another treatment process includes monoclonal antibody therapy which has been found to be effective for treating acute promyelocytic leukemia.
Haemolytic disease of the foetus and new born which is also termed as erythroblastosis fetalis is the alloimmune condition which is developed in foetus during birth. It occurs when IgG molecules that are produced in mother is passed on to the foetus through placenta. Among the antibodies that are passed some attacks the antigens on the red blood cell of the foetus in foetal circulation and breaks down destroying those cells. As a result, the foetus might develop reticulocytotic and anemia. Intensity of this disease varies from mild to severe which can ultimately lead to death of the foetus due to heart failure (Nassar & Wehbe, 2018). During moderate and severe cases of erythroblastosis fetalis, excessive immature erythroblasts are present in the blood of the foetus.
Antibodies are usually produced if the body is being exposed to foreign antigen to fight against it. When a pregnant mother is exposed to such type of foreign antigen the immune system of the mother produces the IgG antibodies that woods targets foreign antigen. These antibodies when passed the unborn through placenta, it attacks the red blood cells of the foetus causing foetal maternal hemorrhage. There are three frequently observed method during which the pregnant mother is sensitised towards foreign antigen which includes blood transfusion, incompatibility of blood group and hemorrhage (Heerema-McKenney, 2022).
Figure: Haemolytic disease of the foetus and new born (Nassar & Wehbe, 2018)
Foetal maternal hemorrhage occurs during the movement of the foetal blood cells cross placenta which might occur during childbirth, abortion, rapture of pleasant and ectopic pregnancy. In most of the cases it has been observed that, the pregnant women might have received blood transfusion due to therapeutic intervention (Vossoughi & Spitalnik, 2019). Although identification of the blood group and the Rhesus system are done prior to the transfusion process, however sometimes due to some negligence incompatibility of the blood group might result in the stated condition. Another reason for the occurrence of blood group incompatibility is observed if the blood group of the mother and the father are incompatible with each other (Patil et al., 2021). As a result, the foetus might possess the blood group characteristics of the father which results in the incompatibility of blood group with the mother. As a result, the immune system of the mother produces antibodies against the antigen present in the foetal blood causing agglutination reaction. This might result from haemolytic disease of the new born.
Treatment of Acute Promyelocytic Leukemia
There are different methods for preventing haemolytic disease in new-borns. These includes immunoglobulin therapy for preventing sensitization reaction in the mother. However, this can only be done in case of Rho immunoglobulin only and not for any other type of blood group incompatibility. In early pregnancy, IVIG or intravenous immunoglobulin tell me administered in case of elevated maternal titers and prior loss also termed as aggressive antibodies. Plasmapheresis if done at early pregnancy would help to reduce maternal titer my replacing and removing plasma antibodies (Agarwal et al., 2019). These two therapies can be done for women with previous history of hydropic fetuses as well as foetal losses.
Intrauterine transfusion can be done by either intraperitoneal transfusion or by intravenous transfusion. In most of the cases the physician prefers intravenous transfusion over intraperitoneal transfusion and is done until 36 weeks of pregnancy (Nassar & Wehbe, 2018). Administering steroids are another method prescribed to pregnant women before the intrauterine transfusion process and during early delivery for maturing the lungs of the foetus. Phenobarbital is really given to pregnant ladies which would help to mature the liver of the foetus and reduce the chance of developing hyperbilirubinemia (Vossoughi & Spitalnik, 2019).
If there is a suspected chance of developing haemolytic disease in the foetus, emergency delivery is to be done by inducing labour to avoid the initiation of the disease. Babies who are born with erythroblastosis fetalis is to be monitored for about 3 to 5 months to observe signs of developing anemia (Nassar & Wehbe, 2018). The babies might require blood transfusion additionally after their birth. With proper prenatal and postpartum care is provided to the baby, erythroblastosis fetalis could be prevented and long-term complication can be avoided (Heerema-McKenney, 2022). The management of the condition can be done by blood transfusion to prevent anemia in the baby along with some immunotherapy which would help to reduce the chance of breakdown of the red blood cells. It would also help to reduce the bilirubin that is 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)
Order an Essay Now & Get These Features For Free:
Turnitin Report
Formatting
Title Page
Citation
Outline
