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Acute lymphoblastic leukemia is what causes?The occurrence and development of leukemia cells derived from different progenitor cells or stem cells become malignant, a specific ALL subtype may have a specific phase of the signs, etiology and pathogenesis have not yet fully clear, but with the following risk factors:
1. Genetic and familial factors in many of the facts proved that genetic factors are a risk factor for leukemia, 5% ALL cases related to genetic factors, some patients have a genetic predisposition syndrome increased incidence of leukemia, Down syndrome, the risk of leukemia in children higher than the 10 to 30 times the normal population, and more likely to have B cell precursor ALL; Fanconi (Fanconi) patients with anemia increased incidence of leukemia.
Occurred in the same family, 2 or 3 cases of leukemia is relatively rare, suggesting that genetic factors in the pathogenesis of ALL may play a small role only, but a twin brother, leukemia, another 1 year, 20% chance of suffering from leukemia, If the leukemia is in place within 1 year of age, and the other will be almost impossible to avoid the occurrence of leukemia, typically occurring in a few months, one of extraordinary twins of their compatriots, such as leukemia is a normal risk of leukemia among 2 to 4 times the mechanism of chromosomal abnormalities is not clear Leukemia merger, probably due to the involvement of protein-coding genes affected the stability and DNA repair genes, or chromosomal


defects increased sensitivity to the carcinogen, which lead to control of cell proliferation and differentiation of gene mutation.
2. Environmental factors of ionizing radiation can induce leukemia in experimental animals; pregnancy diagnostic X ray exposure, the occurrence of a slightly increased risk of ALL, and with the number of relevant exposure; to have suffered nuclear radiation significantly increased incidence of ALL people, ionizing radiation as the human one of the causes of leukemia has been affirmed, but the mechanism is unclear, exposure to pesticides before pregnancy and during pregnancy, active and passive smoking may be related to the pathogenesis of ALL children; children ALL the higher incidence in industrialized countries; women drinking TCE pollution, water quality and smokers older than 60 years of age increased the incidence of ALL, suggesting that environmental factors play a role in the pathogenesis of leukemia.
Animal experimental chemical induced leukemia has been identified, including benzene and benzene congeners, alkylating agent is considered close to human leukemia, and leukemia-related biological factors, the virus accounted for the most important position, the virus as the cause of animal leukemia One has confirmed the 20th century, 80 from adult T cell leukemia cell lines that C-type retrovirus, the human T cell leukemia virus type (HTLV-I), which is found the first human leukemia and lymphoma retrovirus-related, but lymphocytic leukemia leukemia virus and the relationship between the experimental results have not yet reliable.
These factors can not fully explain the etiology of all cases, although there are many clues, but in most cases the risk factors remain unclear, the general that the incidence of leukemia, reflects a variety of genetic and environmental factors interact.
3. Acquired genetic change all ALL cases leukemic cells have acquired genetic changes, at least 2 / 3 of the non-random, including changes in chromosome number and structure, which includes translocation (the most common exception), inversion , deletion, point mutation and duplication, rearrangement of these genes, interfering with normal cell differentiation, proliferation, and survival.There are two mechanisms of leukemia, one dependent on the proto-oncogene or a proto-oncogene activation characteristics of the hybrid gene, the resulting protein products affect cell function; Another mechanism is one or more tumor suppressor genes inactivation, such as p53, INK4a, p16 and encoding p19ARF, p53 as a tumor suppressor gene that can not be repaired after DNA damage cell apoptosis, MDM-2 oncogene antagonist, is the p63 gene, and its overexpression can prevent the wild-type p53 function has been found in leukemia two abnormal genes, p16 and p19ARF negative regulator of cell cycle, reducing the proportion of S phase cells, therefore, can not stop the proliferation of leukemic cells or to prevent programmed cell death, the loss of tumor suppressor function, p15 and p16 deletions in 20% homology to 30% of the B cell precursor ALL and 60% to 80% of the T-ALL can be measured in that study confirmed that, p15 / p16 deletions in ALL relapse can often be seen, suggesting that the missing genes encodes a protein role in disease development.
ALL of the basic pathological changes are mainly manifested as proliferation and infiltration of leukemic cells, this is the specific pathological changes of leukemia, in addition to the hematopoietic system, other organizations such as the liver, brain, testes, kidney and other organizations also apparent infiltration and destruction.
1. Bone marrow, lymph nodes, liver, spleen is the main organ involved.
Most of the bone marrow showed a proliferation of leukemia cells showed diffuse proliferation and infiltration of sheets, with varying degrees of differentiation and maturation arrest, the body has leukemia cell proliferation of bone marrow infiltration, vertebrae, sternum, pelvis and ribs most obvious infiltration of a small number of bone marrow proliferation is low, may be associated with varying degrees of fibrosis.
Lymph nodes is more common (about 70%), usually generalized or multiple of the lymph nodes, lymph node is the early involvement of lymph node structure can still be identified, often involving only the leukemia cells of a lymph node area, appears flaky proliferation of naive uniform infiltration, leaching Basso widened, sinus narrow, the primary follicles or secondary follicles to shrink by squeezing and Late lymph node structures are completely destroyed.
Different degree of spleen enlargement, microscopic diffusion of white pulp with infiltration of leukemia cells can spto the red pulp and sinusoids, liver infiltration of leukemia cells mainly around the portal area and portal area, resulting in hepatomegaly.
Tonsils, the thymus was often invaded, ALL thymus involvement accounted for 78.5%, of which the most common T-ALL, by increasing infiltration of the thymus, clinical manifestations of mediastinal mass, especially when the swelling of T-ALL children are more significant.
2. The nervous system nervous system is the common site of leukemic infiltration, ALL with central nervous system injury more common than other types of leukemia, pathological changes mainly meninges and brain parenchyma or diffuse leukemic cell infiltration of the limitations may be associated with bleeding, hematoma , meningitis, and epidural mass formation of the cross section of spinal cord inflammation, subarachnoid involvement common in parts of the brain substance were involved cerebral hemisphere, basal ganglia, brain stem and cerebellum, the lesion was diffuse leukemic cells or nodular infiltration, infiltration of white matter surrounding tissue edema and necrosis, approximately 20% of the central nervous system leukemia (CNS-L) in patients with cranial nerve palsy, the facial nerve ( ) paralysis of the most common, followed by outreach ( ), eye ( ), trochlear (IV) nerve, and spinal cord and peripheral nerve involvement is rare.
3. Urogenital ALL violations of testosterone are more common, especially children, ALL, Leydig cell infiltration seen in a large number of leukemia, caused by compression fine tubular atrophy, clinical manifestations of unilateral or bilateral painless testicular swelling, bulge sense of corpus cavernosum infiltration of leukemia cells or leukemia cells in the sinus due to siltation, thrombosis, blood flow obstruction or thrombosis can cause sustained priapism penis, ALL those involving the kidney, renal capsule, and visible white spots or nodules bleeding, pelvic bleeding are more common, skin, white nodules scattered in the medulla, microscope, cortex and medulla scattered or focal leukemic cell infiltration, glomerular and renal tubular epithelial atrophy or pressure necrosis.
4. Other often involving the lungs to the organs of leukemia, one of most diffuse infiltration of lesions, a small number of the formation of miliary, nodular lesions or even be invaded, and the alveoli, small blood vessels and interstitial lung, leukemia, most commonly involving the bronchial lymph node infiltration can cause pressure, but also involving the pleura, showed varying degrees of diffuse infiltration, pleural effusion occurred; easy to violations of the oropharynx is the site of one of the ALL, and is often associated with infection; leukemia involving the heart to myocardial infiltration, myocardial , muscle bundle between the diffuse and focal infiltration, leading to conduction disturbances, heart failure, involving both epicardial and endometrial, there pericardial effusion, infiltration of the gastrointestinal tract can form nodules, ulcers, necrosis and bleeding, the mucosa and submucosa mainly mucosal exfoliation can sometimes occur, and pseudomembrane formation, the lesion may be due to necrosis and perforation of intestine, from the cardia to the rectum can be involved, who invaded the lower esophagus, skin involvement typical change in the perivascular , hair follicles and sebaceous glands of the leukemic cell infiltration, the formation of single or multiple nodules, showing focal distribution.
Leukemia hematopoietic progenitor cells or by a malignant stem cells from the reasons are: almost all ALL leukemia cells were immunoglobulin (Ig) or T cell receptor (TCR) gene rearrangement cloning and expression; All the same patient leukemic cells have the same cytogenetic abnormalities, glucose 6 - phosphate dehydrogenase (G-6PD) isoenzyme type and phenotype; most complete remission (CR) of the patients relapse, the leukemic cells of genotype and phenotype reproduction diagnosis of cloning.
A large number of leukemia cells and normal hematopoietic cells inhibit the proliferation of the exact mechanism has not yet determined, but the growth factor, normal and leukemic cell growth factor receptor, and the response of growth factor receptors on the two types of cells have an important role in proliferation and inhibition of the growth factor receptor, or spto the nucleus from the cell membrane growth factor transcription signals, the expression of leukemia cells are encoded by oncogenes, it was observed that leukemia cells can produce colony stimulating factor (CSF), this may be an infinite proliferation of leukemic cells; a few kinds of normal CSF clone of leukemia cells in vitro were stimulated; surrounding red blood cells, thrombocytopenia, bone marrow leukemia cells is dominated by common hematological characteristics of acute leukemia, suggesting that the normal hematopoietic stem cells are excluded due to leukemia cells, However, some patients with myeloproliferative low, it is difficult to explain with the leukemia cells crowd out that the leukemia cells through cell-mediated or humoral mechanisms of inhibition of normal hematopoietic cells, leukemia cells was confirmed in the extract or the medium has an inhibitory activity of substances, specifically inhibition of DNA synthesis in progenitor cells of the normal colony forming units (CFU-C); a variety of lymphoblastic leukemia with a large number of leukemia cell surface interleukin -2 receptor (IL-2R), which may be the closure factor blocking IL -2 combined with normal activated lymphocytes, the activity of normal lymphocytes and lymphokine release, thus contributing to the proliferation of leukemia cells.



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