Acute Lymphoblastic Leukemia - Research Paper Example

? Acute Lymphoblastic Leukemia Acute Lymphoblastic Leukemia Leukemia is a malignant disease that affects the hematopoietic system. Ifthe overproliferation of immature leukocyte is evident, it is called acute leukemia, whereas well differentiated leukocytes are found in chronic leukemia (Dorantes-Acosta et al., 2009). Acute Lymphoblastic Leukemia, or ALL, is the most common malignant carcinoma in pediatric patients (Cipoloti et al., 2003). It is characterized by abnormal proliferation of leukemic blasts that are poorly differentiated, leading to inadequate hematopoiesis (Siddique et al., 2011). Pathogenesis There are several studies that dissect the underlying cellular events responsible for acute lymphoblastic leukemia. The basic mechanism for abnormal proliferation of any cell remains the same. The cell cycle consists of different phases with various check points to control abnormal division. The most important are the transition from G1 to S phase and G2 to M phase. Division of cell only takes place after receiving instructions from some external stimulation (Cipoloti et al., 2003). There are various mechanisms by which cells are regulated for division. This includes stimulation from special molecules called mitogenic substances, inhibition by various anti-proliferative cytokines and regulation by adjacent cells. Most of the cancer cells including those involved in ALL, abandon these regulatory mechanisms. Various studies including one by Cipoloti et al. tried to isolate mutations in those tumor suppressor genes that are responsible for keeping a check during cellular division. An example is the inactivation of p15 gene in children with acute lymphoblastic leukemia. P15 and other related genes are responsible for producing cyclic inhibitors that bind to CD 4 and 6. This binding triggers various complex events that include phosphorylation of Rb protein which, in turn, inhibits cell cycle progression (Cipoloti et al., 2003). Therefore, deletion of this important tumor suppressor gene can lead to abnormal proliferation of leukocytes and, thus, constitute a major factor in the development of acute lymphocytic leukemia. Another study (Lin et al., 2012) demonstrated mutation in one of the signaling pathways and its role in development of acute lymphoblastic leukemia in Chinese patients. According to the report, Notch 1 is a signaling pathway crucial for the development of T-cells and its mutation is found commonly in patients with ALL. To verify the extent of this abnormal expression, real time PCR was used to detect the gene and its mutation. It was evident in the results that most patients had overexpression of Notch 1 gene that contributed to overproliferation of T cells in ALL (Lin et al., 2012). Subtypes It is important to remember that there is no single cause of cancerous growth of cells in ALL, but various factors unite together and lead to this abnormal proliferation. Moreover, there are various subtypes within ALL, such as precursor B-Cell and T-Cell leukemia. All these subgroups show some variation in their pathogenesis. A study by Teuffel et al. in 2008 focused on anemia and survival in children suffering from various subtypes of acute lymphoblastic leukemia. In the above mentioned cohort study, 1162 patients were analyzed for the subtype of ALL and their associated Hb levels. It was evident that patients with the T cell subtype had a higher level of hemoglobin as compared to the B cell precursor type. Moreover, less severe anemia was associated with an increased survival rate in early childhood. This explains that various subtypes have different impacts on the hematopoietic system and, therefore, variable survival rate. Risk Factors Few risk factors have been isolated for acute lymphoblastic leukemia. Those which are assumed to be associated with ALL are poorly verified and contain diverse controversial evidence. A matched control case study found that increased maternal age is associated with increased incidence of ALL. Paternal age showed no association and only a weak link was identified with a number of older siblings, which suggested that disease manifestation was only delayed with no effect on the incidence rate (Feller et al., 2010). Signs and Symptoms Patients suffering from acute lymphocytic leukemia present variable signs and symptoms depending on the severity of the disease. Most of these symptoms are associated with bone marrow failure. It is ironic because a huge number of white blood cells are produced in ALL, but unfortunately they are abnormal and interfere with the production of other blood cells such as red blood cells. So the patients can present with anemia and associated symptoms of shortness of breath, fatigue and pallor. Other symptoms include bone pain, frequent infections and bleeding from gums or nose. Some other extra medullary symptoms are present in some rare cases. These include obstructive jaundice and cutaneous involvement. A case report (Siddique et al., 2011) highlighted presence of obstructive jaundice in one patient diagnosed with acute lymphoblastic leukemia. Upon work up, it was evident that patient was normal for other hepatocellular etiologies of jaundice. Therefore, in those patients that present with jaundice and have inconclusive initial work up, ALL should be considered (Siddique et al., 2011). Although rarely, ALL can present with cutaneous involvement evident as red indurated nodules (Bay et al, 2004). These lesions are produced by cutaneous infiltration of malignant cells. Diagnosis There are several workups that can be done to identify acute lymphocytic leukemia. These include complete blood count which may show increased WBC count (leukocytosis) and decreased hemoglobin (Simon, 2012). Peripheral blood smear can be done, most likely showing leukocytic blast cells. Although these tests can be done as initial work up, bone marrow biopsy remains a gold standard procedure to confirm the diagnosis (Simon, 2012). Bone marrow aspiration viewed under the microscope will show leukocytic blast cells of either B cell or T cell origin. Imaging studies can be done to determine the extent of spread. Other leukemia and hematological disorders may present similarly and can be included in differential diagnosis. Treatment There are four phases of ALL treatment: induction, consolidation, maintenance and prevention. Chemotherpay is the mainstay for treating any leukemia. There are certain protocols for chemotherapy that shows variable outcome. One such example is the St Jude Total XIII remission induction treatment protocol (Bay et al., 2004). L-asparaginase (L-Asp) is mostly used as an adjunct with chemotherapy (Tanaka et al., 2012). Bone marrow stem cell transplant has shown some promising results, but still there are many hurdles before this treatment option can be widely available. Apart from using these drug regimes, patient should also be educated regarding the disease for self care as part of the management plan. As ALL affects the immune cells, patient should be advised to avoid pathogens and practice extreme hygiene if possible. Most of the patients get this disease in the first decade so providing appropriate counseling to them and their parents can be very beneficial. Prognosis With the current risk adapted treatment, ALL has 80% event free survival rate of 5 years and 8 year survival rate of about 90% (Iughetti et al., 2012). References Bay, A., Oner, A. F., Tuncer, O., Atas, B., Yuca, S., & Erol, M. (2004). Case report - acute lymphoblastic leukemia presenting with cutaneous involvement. European Journal of General Medicine, 1(2). Medical Investigations Society. Cipolotti, R., Lemos, J. A. R., Defavery, R., Scrideli, C. A., Dal Fabbro, A. L., & Tone, L. G. (2003). Inactivation of the p15 gene in children with acute lymphoblastic leukemia. Sao Paulo Medical Journal, 121(5). Dorantes-Acosta, E., Arreguin-Gonzalez, F., Rodriguez-Osorio, C. A., Sadowinski, S., Pelayo, R., & Medina-Sanson, A. (2009). Acute myelogenous leukemia switch lineage upon relapse to acute lymphoblastic leukemia: a case report. BioMed Central Ltd. Feller, M., Adam, M., Zwahlen, M., Brazzola, P., Niggli, F., & Kuehni, C. (2010). Family characteristics as risk factors for childhood acute lymphoblastic leukemia: A population-based case-control study. Public Library of Science. doi/10.1371/journal.pone.0013156. Iughetti, L., Bruzzi, P., Predieri, B., & Paolucci, P. (2012). Obesity in patients with acute lymphoblastic leukemia in childhood. BioMed Central Ltd. Lin, C., Zheng, H., Wang, C., Yang, L., Chen, S., Li, B., Zhou, Y.... Li, Y. (2012). Mutations increased overexpression of Notch1 in T-cell acute lymphoblastic leukemia. BioMed Central Ltd. Siddique, M. N., Popalzai, M., Aoun, N., Maroun, R., Awasum, M., & Dai, Q. (2011). Precursor B-cell acute lymphoblastic leukemia presenting as obstructive jaundice: A case report. BioMed Central Ltd. Simon, H. (2012, July 7). Acute Lymphoblastic Leukemia. The New York Times. Retrieved from http://health.nytimes.com/health/guides/disease/acute-lymphocytic-leukemia-all/diagnosis.html Tanaka, R., Osumi, T., Miharu, M., Ishii, T., Hasegawa, T., Takahashi, T., & Shimada, H. (2012). Hypoglycemia associated with L-asparaginase in acute lymphoblastic leukemia treatment: A case report. BioMed Central Ltd. Teuffel, O., Stanulla, M., Cario, G., Ludwig, W. D., Rottgers, S., Schafer, B. W., Zimmermann, M., & Niggli, F. K. (2008). Anemia and survival in childhood acute lymphoblastic leukemia. Ferrata Storti Foundation. doi/10.3324/haematol.13156. Read More