Leukemia is a group of cancers that typically starts in the bone marrow and results in high number of abnormal white blood cells.
Acute Lymphoblastic Leukemia (ALL)
ALL is an acute form of leukemia (cancer of the white blood cells) characterized by the overproduction and accumulation of ancerous, immature white blood cells (lymphoblasts). In ALL, lymphoblasts are overproduced in the bone marrow and continuously multiply, causing damage and death by inhibiting the produciton of normal cells such as red blood cells, other white blood cells and platelets. ALL is most common in childhood with a peak incidence at 2-5 years of age, and another peak in old age.
Cuases: The efinitive cause of most cases of B cell ALL is not known, although in many cases, the disease results from acquired genetic alterations in the DNA of a single cell, causing it to become abnormal and multiply continously. (Hagal, WO 02/059264)
Symptoms: include fever, increased risk of infection, shortness of breath, chest pain, cough, vomiting, and changes in bowel or bladder habits, increased tenedcy to bleed (due to thrombocytopenia) and signs indicative of anemia such as pallor, tachycardia (high heart rate), fatigue and headache. These sytpoms are indicative of a reduced production of functional blood cells, because the leukemia wastes the resources of the bone marrow, which are normally used to produce new fuunctioning blood cells.
Diagnosis: begins with physical examination, complete blood count and blood smears. Bast cells are seen on blood smear in the majority of casesA bone marrow biopsy is conclusive proof of ALL. Pathological examination, cytogenetics such as the presence of the Philadelphia chromosome and immunophenotyping establish whether myloblastic (neutrophils, eosinophils or basophils) or lymphoblastic (B or T lymphocytes) are the problem.
Acute Myeloid Leukemia (AML)
AML is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal whtie blood cells that accumulate in the bone marrow and interferes with the production of normal blood cells. AML is the most common acute leukemia affecting adults, and its incidence increases with age. It accounts for about 1.2% of cancer deaths in the US
Symptoms: include fatigue, shortness of breath, easy bruising and bleeding, and increased risk of infection. The syptoms are caused by replacement of normal bone marrow with leukemic cells, which causes a drop in red blood cells, platelets and normal white blood cells. A lack of normal white blood cell production makes the patient susceptible to infections, while the leukemic cells themselves have no infeciton fighting capacity. A drop in red blood cell count (anemia) can cause fatigue, paleness and shortness of breath. A lack of platelets can lead to easy brusing or bleeding with minor trauma.
Some patients with AML may experience swelling of the gums because of infiltration of leukemic cells into the gum tissue. Rarely, the first sign of leukemia may be the development of a solid luekmic mass or tumor outside of the bone marrow, called a chloroma.
Detection: An abnormal result on a complete blood count is a first sign of AML. An excess of abnormal white blood cells (leukocytosis) is a common finding. AML can also present with isolated decreases in platelets, red blood cells or even with a low white blood cell count (leukpenia). A presumptive diagnosis of AML can be made via examination of a peripheral blood smear when there are cirulating leukemic blasts. A definitive diagnosis usually requires an adequate bone marrow aspiration and biopsy.
Marrow or blood is exmained via ligh microscopy as well as flow cytometry to diagnose the presence of leukemia and to differentiate AML from other types of leukemia such as acute lymphblastic luekemia (ALL) and to also classify the subtye of disease.
Treatment: varies among subtypes. AML is treated initial with chemotherapy aimed at inducing a remission. Patients may go on to receive additional chemotherapy or a hematopoietic stem cell transplant.
Chronic Myelogenous Luekemia (CML)
The Philadelphia chromosome is a genetic abnormality in chromosome 22 in luekemia cells. The gene is the ABL1 gene of chromosome 9 justaposed onto the BCR gene on chromosome 22 coding for a hybrid protein; a tyrosome kinase signalling protein which is always “turned on” as a result of the abnormality, causing the cell to divide uncontrallably.
Treatments:
–Tyrosine kinase inhibitors:
—-Imatinib (Glivec): was approved by the FDA in 2001 for the treatment of chronic myelogenous leukemia (CML), a rare form of cancer that affects certain type of white blood cells. Since approval, its use has been approved for pateitns with several types of gastrointestinal tumors. The drug has been described as a miracle drug in that it has a phenomenal success rate. Its development started in the late 1950s when researches notice that cancer cells chromosomal abnormality in that individuals with CML had an atypical small chromosome #22 which was called the “philadelphia chromosome”. The long arm had transferred to chromosome 9. Ten years later scientists determined the actual genes involved in the translocation labeled as human c-abl oncogene located in the region of chromosome 9 that translocates to become part of the Philadelphia chromosome. Then, the scientists idnetifed a breakpoint cluster region in which all of chromosome 22 breaponts seemed to occur in CML pateitns. Later scientists from the Whitehead Institute in Cambridge infected bone marrow cells with a retrovirus encoding the fusion gene and demonstrated that the presence of an iactive bcr-abl gene initials CML like symptoms. Later researches identified the fuction of the bcr-abl fusion gene: production of an abnormal tyrosine kinase protein that is not properly regulated. This proliferation resutls int he overproduction and accumulation of immature white blood cells, which is the ahllmoark of CML. Research at Ciba-Geigy (which later become Novartis) identified kinase blocking inhibitors using computer models to predict which molecule structures might fit the ATP binding site of the fusion protein. One compound was particularly pormosing. kills cancer cells by turning of tyrosine kinase. It is marketed by Novartis. It is on the World Health Orgnization List of essential medicines.