leukemia causes / Leukemia - Causes and Symptoms

Leukemia - Causes and Symptoms





Leukemia is a term that includes a series of malignant diseases, commonly called "blood tumors"; these are neoplastic hyperproliferations affecting hematopoietic stem cells, bone marrow and lymphatic system.

Leukemia Symptoms From a clinical point of view and based on the rate of progression, leukemia is distinct in acute (severe and sudden) or chronic (it slowly exacerbates over time).

Another important classification depends on the cells from which the neoplasia originates: it is called lymphoid leukemia (or lymphocytic, lymphoblastic, lymphatic), when the tumor affects the intermediate precursors of T or B lymphocytes and myeloid leukemia (or myeloblastic, myelocytic, granulocytic), when, instead, the degeneration concerns the common progenitor of granulocytes, monocytes, erythrocytes and platelets.

Based on these considerations, we will have four common types of leukemia: chronic myeloid leukemia (CML) and acute myeloid leukemia (AML); chronic lymphatic leukemia (LLC, also called lymphocytic) and acute lymphatic leukemia (LLA, also called lymphoblastic).
Causes

The causes of leukemia are not known, although it is now evident that the pathology, like other tumors, is the end result of a complex series of events, involving both constitutional genetic factors and environmental factors (ionizing radiation, toxic substances such as benzene derivatives, infectious agents ...). The uncontrolled proliferation of leukemic cells is the result of an anomaly in the DNA, which - as indeed in other types of neoplasia - determines an alteration of the mechanisms of regulation and control of growth and cell differentiation. These processes are regulated by specific genes that, if they suffer damage, can determine the transformation of a cell from normal to neoplastic, according to only partially known events.

Although the causes are still not completely clear, certain myelotoxic agents (benzene, alkylating agents and ionizing radiations) have been identified with certainty, which may favor leukemogenesis.

The main risk factors, which can facilitate the onset of the leukemic forms, are:

    Exposure to high doses of ionizing radiation, which can occur by:

        Radiotherapy: the incidence is very high in subjects treated with radiotherapy for other neoplasms; in this case the blood tumors are defined secondary.
        Atomic accidents: to remember is the tragic balance between the survivors of the atomic explosions of Hiroshima and Nagasaki, exposed to high doses of radiation and severely affected by leukemia.

    Occupational exposure: it is possible that there is an association between leukemia and prolonged exposure to radiation, to some chemicals in the workplace and at home, or to low-frequency electromagnetic fields; however, there is no definitive evidence yet to demonstrate its close correlation.
    Benzene: used in the chemical industry, present in oil and petrol. Its prolonged inhalation over time is associated initially with haematological dyscrasia (alteration of the relationships of the elements that compose the blood or other organic liquids), which can degenerate into leukemia. To exert mutagenic and carcinogenic action, benzene must undergo oxidative conversion and turn into reactive intermediates that react covalently with DNA, causing interference with replicative and nucleic acid repair processes.
    Intake of antiblastic, type II topoisomerase inhibitors and some chemotherapeutic drugs may increase the risk of secondary leukemia (especially in combination with radiotherapy). The agents that induce greater susceptibility are alkylating agents (chlorambucil, nitrosoureas, cyclophosphamide).
    Smoking may contribute to the onset of some forms of leukemia (1/4 of all acute myeloid leukemia occur among smokers), due to the presence of some substances contained in the cigarette, such as benzopyrene, toxic aldehydes and certain heavy metals (example : cadmium and lead).


Some inherited diseases - such as Down syndrome or chromosomal instability syndromes - are related to a 10-20-fold risk of developing leukemia in the first ten years of life. In some of these diseases, genetic mutation directly involves particular proteins implicated in DNA repair processes. The risk of developing a leukemia is therefore related to a lower cellular efficiency in the mechanisms of protection in the case of genetic alterations.
    Myelodysplasia (preleukemic pathology) and other predisposing blood diseases: make it more susceptible to the onset of acute myeloid leukemia.
    Man-type T lymphocyte viruses (HTLV-1): are a class of retroviruses oncogenes (classified as oncoviruses), also called human T-cell Leukemia Virus (Human T-cell Leukemia Virus), capable of to provoke, in rare cases, leukemia and lymphoma of the adult, and to promote cell proliferation in an indirect way: the virus replicates slowly and remains very long latent in the infected cells, mainly T lymphocytes. HTLV-1 infection is implicated in particular in chronic lymphoblastic leukemia (LLC).
    Family transmission: only in rare cases a patient with leukemia (chronic lymphatics, in particular) has a parent, a brother or a child suffering from the same disease.

Exposure to one or more risk factors potentially implicated in leukemogenesis does not necessarily cause the onset of the disease. Furthermore, it is important to remember that in the pathogenesis of the different types of leukemia specific chromosomal alterations occur, which allow to characterize the different neoplastic forms, such as translocation t (9; 22), with the formation of the Philadelphia chromosome, in chronic myeloid leukemia or trisomy of chromosome 12, common in patients with chronic lymphocytic leukemia. During the diagnosis, the identification of specific aberrations of genes and chromosomes, using conventional cytogenetic techniques, in situ hybridization or molecular biology, makes it possible to identify the subtype of leukemia and guide towards the therapeutic choice.
Symptoms

To deepen: Leukemia Symptoms

The disorders and symptoms of leukemia may vary in each patient, depending on the type and amount of cancer cells, and the severity of the disease. In some cases, in the initial stages the symptoms may be non-specific and may be caused by other concomitant diseases.
Because of the proliferative advantage of the leukemic cells, a clonal expansion takes place that occupies most of the bone marrow and pours into the bloodstream. The invasive character of the neoplastic clones also allows their diffusion to the lymphatic glands or to other organs (example: spleen) and can cause swelling or pain in various parts of the body.

Patients with chronic leukemia may be asymptomatic and the doctor may detect clinical signs during a routine blood test, while patients with an acute form of the disease often undergo a medical examination due to a sensation general of malaise.

Therefore, the general symptoms that can develop include:

    Fatigue and general malaise (asthenia), caused by the reduced production of red blood cells;
    Vagus abdominal disorders, with loss of appetite and weight;
    Fever, due to the disease itself or a concomitant infection (favored by the decrease in white blood cells by the bone marrow);
    Joint or muscular pain (in case of considerable tumor mass). Furthermore, a characteristic bone pain due to the compression exerting the expanding bone marrow can occur;
    Excessive sweats, especially at night;
    Dyspnoea (from lack of red blood cells), palpitations (from anemia).

Symptoms caused by the infiltration of blasts in the bone marrow:

    Tendency to have bruising or bleeding (due to the decrease in the production of platelets, the blood elements responsible for the coagulation). In general, the loss of blood is mild and typically occurs in the skin and mucous membranes, with bleeding from the gums, the nose or the presence of blood in the stool or urine;
    Increased susceptibility to infections, usually caused by decreased production of functioning leukocytes. Infections can affect every organ or apparatus and are accompanied by headache, fever and rash;


Anemia and related symptoms such as weakness, easy fatigue and skin pallor.

Symptoms of leukemia caused by infiltration into other organs and / or tissues:

    Lymphadenopathy (swelling of the lymph nodes) especially latero-cervical, axillary, inguinal;
    Pain in the left side (under the rib arch) due to enlargement of the spleen (splenomegaly);
    Possible enlargement of the liver;
    Infiltration of the central nervous system (rare): leukemic cells can invade the brain, spinal cord or meninges. In case this event occurs, the patient can observe:
        Headache, associated or not with nausea and vomiting;
        Alterations in the perception of sensitivity, such as numbness or tingling in various parts of the body;
        Paralysis of the cranial nerves, with impaired vision, fall of the eyelid, deviation of the angle of the mouth.

In the advanced stages the accentuation of the above mentioned symptoms can occur and the clinical manifestations of the leukemia can include:

    Sudden febrile ups;
    Altered state of consciousness;
    Convulsions;
    Inability to speak or move the limbs.

In the event of symptoms such as high fever, sudden bleeding or convulsions without an apparent cause, emergency treatment for acute leukemia is essential.
If signs of recurrence, such as an infection or hemorrhage, are present during disease remission (attenuation or disappearance of symptoms of a disease), it is necessary to undergo a medical check-up.