Acute lymphoblastic leukemia

Introduction Acute lymphoblastic leukemia (ALL) is a malignant neoplastic disease in which B-lineage or T-lineage cells originating from lymphocytes are abnormally proliferating in the bone marrow. The abnormally proliferating primordial cells can aggregate in the bone marrow and inhibit normal hematopoietic function, and can also invade tissues outside the bone marrow, such as meninges, lymph nodes, gonads, and liver. China has conducted a survey of the incidence of leukemia, the incidence of ALL is about 0.67 / 100,000. The incidence rate in oil fields and contaminated areas is significantly higher than the national incidence rate. ALL childhood (0 to 9 years old) is the peak incidence, which can account for more than 70% of childhood leukemia. ALL accounts for about 20% of adult leukemia in adults. At present, according to the different biological characteristics of ALL, the corresponding treatment plan has achieved good curative effect. About 80% of children and 30% of adults can obtain long-term disease-free survival and have the possibility of cure. Causes (1) Pathogenesis The occurrence and development of leukemia cells originate from the malignant transformation of different hematopoietic progenitor cells or stem cells. The specific ALL subtype may have specific stage markers. The etiology and pathogenesis are not fully understood, but are related to the following risk factors. : 1. Genetic and family factors: Many facts prove that genetic factors are one of the risk factors for leukemia, 5% of ALL cases are related to genetic factors, some patients with genetic predisposition syndrome have an increased incidence of leukemia, and children with Down syndrome have leukemia. The risk is 10 to 30 times higher than that of the normal population, and it is more likely to have B cell precursor ALL, and the incidence of leukemia in patients with Fanconi anemia is also increased. Cases of 2 or 3 leukemias in the same family are rare, suggesting that genetic factors may only play a minor role in the pathogenesis of ALL, but when a twin brother develops leukemia, another 20% chance of developing leukemia within 1 year. If leukemia occurs within 1 year of age, another is almost inevitable, and leukemia will occur. Typically, it occurs within a few months. One of the non-identical twins, such as leukemia, has a normal incidence of leukemia. 2 to 4 times, the mechanism of chromosomal abnormalities with leukemia is still unclear. The reason may be that the protein encoded by the affected gene affects the stability of the gene and DNA repair, or the sensitivity of the defective chromosome to carcinogens increases, thus causing The gene that controls cell proliferation and differentiation is caused by mutation. 2. Environmental factors: Ionizing radiation can induce experimental leukemia in animals. It is exposed to diagnostic X-ray during pregnancy. The risk of ALL is slightly increased, and it is related to the number of exposures. After exposure to nuclear radiation, the incidence of ALL is significantly increased. Ionizing radiation is used as One of the causes of human leukemia has been affirmed, but the mechanism is unclear. Pre-pregnancy and pregnancy exposure to pesticides, active and passive smoking may be related to the incidence of childhood ALL. The incidence of childhood ALL is higher in industrialized countries, and women are contaminated with trichloroethylene. The water quality and the incidence of ALL in smokers older than 60 years old increased, suggesting that environmental factors play a role in the pathogenesis of leukemia. Chemical-induced experimental leukemia in animals has been confirmed, among which benzene and benzene congeners, alkylating agents are considered to be closely related to human leukemia. Among the biological factors related to leukemia, viruses account for the most important status, and viruses are the cause of animal leukemia. One has confirmed that in the 1980s, a type C retrovirus, the human T cell leukemia virus type I (HTLV-I), was found from the cell line of adult T cell leukemia, which was the first to be found with human leukemia and Lymphoma-associated retroviruses, but the relationship between leukemia virus and lymphocytic leukemia has not yet yielded reliable experimental results. These factors do not fully explain the cause of the disease in all cases. Although there are many clues, the pathogenesis of most cases remains unclear. It is generally believed that the occurrence of leukemia reflects the interaction between multiple genetic and environmental factors. 3. Acquired genetic alterations: Leukemia cells in all ALL cases have acquired genetic alterations, at least 2/3 are non-random, including changes in chromosome number and structure, the latter including translocation (which is the most common abnormality), Position, deletion, point mutation and duplication, these rearrangements affect the expression of genes, interfere with the differentiation, proliferation and survival of normal cells. (II) Pathogenesis Leukemia usually has two mechanisms, one is dependent on the protooncogene or the activation of a mixed gene with proto-oncogene properties, and the resulting protein product affects cell function. Another mechanism is one or more Inactivation of tumor suppressor genes, such as p53 and INK4a, encoding p16 and p19ARF, p53 as a tumor suppressor gene, causing apoptosis of cells unable to repair after DNA damage, MDM-2 proto-oncogene is an antagonist of p63 gene Overexpression of the agent can prevent the function of wild-type p53. Abnormalities of these two genes have been found in leukemia. P16 and p19ARF negatively regulate the cell cycle and reduce the proportion of cells entering the S phase, thus preventing leukemia cell proliferation. Or can prevent programmed death, loss of tumor suppressive function, p15 and p16 homology deletion can be detected in 20% to 30% of B cell precursor ALL and 60% to 80% of T-ALL, Studies have confirmed that p15/p16 deletion is often seen in the recurrence of ALL, suggesting that the protein encoded by this deletion gene plays a role in disease progression. The basic pathological changes of ALL are mainly the proliferation and infiltration of leukemia cells. This is a specific pathological change of leukemia. In addition to the hematopoietic system, other tissues such as liver, brain, testis, kidney and other tissues also have obvious infiltration and destruction. 1. Bone marrow, lymph nodes, liver, and spleen are the most important organs involved. Most of the bone marrow showed obvious hyperplasia. The leukemia cells showed diffuse flaky hyperplasia and infiltration, with different degrees of differentiation and maturation. The whole body bone marrow had leukemia cell hyperplasia, and the infiltration of vertebrae, sternum, pelvis and ribs was the most obvious. Low proliferation, can be accompanied by varying degrees of fibrosis. Lymph node enlargement is more common (about 70%), generally systemic or multiple lymphadenopathy, early lymph node involvement, lymph node structure is still identifiable, leukemia cells often only involve a certain area of the lymph nodes, appearing flaky Uniform naive cells proliferate and infiltrate, lymph cords widen, sinus narrows, primary follicles or secondary follicles are atrophied by compression, and advanced lymph node structures are completely destroyed. The spleen has different degrees of swelling. The white pulp in the white pulp has diffuse infiltration of leukemia cells, which can affect the red pulp and sinusoids. The leukemia cells in the liver mainly infiltrate the portal vein area and the portal vein area, causing liver enlargement. The tonsils and thymus are often invaded. The ALL thymus is affected by 78.5%. Among them, T-ALL is the most common, and the infiltrated thymus is enlarged. The clinical manifestation is mediastinal mass, especially in children with T-ALL. 2. Nervous system: The nervous system is a common site of leukemia infiltration. The damage of ALL combined with central nervous system is more common than other types of leukemia. The pathological changes are mainly localized or extensive infiltration of meningeal and brain parenchymal leukemia cells, which may be accompanied by hemorrhage. Hematomas, meningitis, and epidural masses of transverse myelitis are common in the subarachnoid space. The brain parenchyma is followed by the cerebral hemisphere, basal ganglia, brainstem and cerebellum. Diffuse or nodular infiltration, infiltration of surrounding white matter tissue edema and necrosis, about 20% of patients with central nervous system leukemia (CNS-L) have cranial nerve palsy, facial nerve (VII) paralysis is most common, followed by abduction ( VI), eye movement (III), trochlear (IV) nerve, and spinal cord and peripheral nerve involvement are rare. 3. Urogenital system: ALL is more common in the testis, especially in children with ALL. There is a large amount of leukemia cells infiltrating in the testicular stroma, which causes atrophy caused by compression of the fine tubules. The clinical manifestations are unilateral or bilateral painless swelling of the testicles. Inflammatory sensation, leukemia cells infiltrating the corpus cavernosum or due to accumulation of leukemia cells in the sinus, embolism, blocked blood flow or thrombosis can cause abnormal erection of the penis, ALL involving the kidney, grayish white spots or nodules visible under the renal capsule And bleeding point, renal pelvis bleeding point is also more common, skin, medulla scattered in grayish white nodules, microscopically seen under the microscope, medulla scattered or focal leukemia cells infiltration, glomerular and tubular epithelial compression atrophy or degeneration and necrosis. 4. Others: The lung is one of the organs often involved in leukemia. Most of the infiltrative lesions are diffuse. A few of them form miliary, even nodular lesions, which can invade the alveoli, small pulmonary vessels and interstitial. Leukemia infiltrates most often involve the bronchi Lymph nodes can cause oppression, but also involve the pleura, diffuse infiltration of varying degrees, and pleural effusion; the oropharynx is also one of the sites that are easily invaded by ALL, and often combined with infection; leukemia involves the heart with myocardial infiltration, Diffuse and focal infiltration between the myocardium and the muscle bundle, leading to conduction disorders, heart failure, epicardial and intima can be involved, pericardial effusion, infiltration of the gastrointestinal tract can form nodules, ulcers, necrosis and hemorrhage, Mucosa and submucosa are the main, sometimes mucosal exfoliation and pseudomembrane formation, lesions of the intestine can be perforated due to necrosis, from the cardia to the rectum can be involved, less invasion of the esophagus, skin invasion typical change to the blood vessels The leukemia cells around the hair follicles and sebaceous glands infiltrate to form single or multiple nodules, which are focally distributed. The reason why leukemia is malignant from a hematopoietic progenitor or stem cell is: 1 Almost all ALL leukemia cells have cloned expression of immunoglobulin (Ig) or T cell receptor (TCR) gene rearrangement. 2 All leukemia cells of the same patient have the same cytogenetic abnormalities, 6-phosphate glucose dehydrogenase (G-6PD) isoenzyme type and immunophenotype. 3 Most patients with complete remission (CR) relapse, their leukemia cell genotype and phenotype reproduce the clone at the time of diagnosis. The exact mechanism of leukemia cell proliferation and normal hematopoietic cell suppression has not been determined, but growth factor, normal and growth factor receptors of leukemia cells, and growth factor receptor reactivity play an important role in the proliferation and inhibition of the two types of cells, growth Factor receptors or growth factor transcription signals from the cell membrane to the nucleus are encoded by oncogenes expressed by leukemia cells. It has been observed that leukemia cells can produce colony-stimulating factor (CSF), which may be related to the infinite proliferation of leukemia cells. Normal CSF has a stimulating effect on leukemia clonal cells in vitro, peripheral red blood cells, thrombocytopenia, and leukemia cells in the bone marrow are dominant. It is a common hematological feature of acute leukemia. It is speculated that due to the exclusion of normal hematopoietic stem cells by leukemia cells, However, some patients have low bone marrow hyperplasia, which is difficult to explain by leukemia cell exclusion. It is believed that leukemia cells inhibit normal hematopoietic cells through cell-mediated or humoral mechanisms, and then it is confirmed that there is an inhibitory active substance in leukemia cell extract or medium, specifically inhibition Normal progenitor colony forming unit (CFU-C) during DNA synthesis, a large number of interleukin-2 receptor (IL-2R) on the surface of leukemia cells with multiple lymphocytic leukemia, which may block IL- as a blocking factor 2 Binding to normal activated lymphocytes affects the activity of normal lymphocytes and the release of lymphokines, thereby facilitating the proliferation of leukemia cells. Clinical manifestations The clinical manifestations of various types of acute leukemia mainly include the manifestations of hematopoietic dysfunction caused by leukemia cell infiltration of bone marrow tissue (such as anemia, infection, hemorrhage, etc.) and systemic infiltration of leukemia cells causing abnormalities of organs (such as lymph nodes, Hepatosplenomegaly, etc.) two major aspects. First, the onset: Most patients have an acute onset, rapid progress, often with fever, anemia or bleeding as the first symptom. Some cases have a slow onset, with progressive anemia as the main performance. Second, the symptoms: (A) anemia: the incidence of anemia, but the severity. (B) bleeding: Most patients have different degrees of bleeding in the course of the disease, with skin defects, ecchymosis, bleeding gums, nasal discharge is common. Severe cases may have visceral bleeding, such as blood in the stool, blood in the urine, hemoptysis and intracranial hemorrhage. (3) Fever: It is one of the common symptoms of acute leukemia. Third, physical signs: (A) liver, spleen, lymph nodes. (B) bone and joint performance: bone and joint pain is a common manifestation, sternal tenderness has a certain value in the diagnosis of leukemia. (C) other signs of infiltration: male testicular involvement can be diffuse enlargement, which is one of the causes of leukemia recurrence. Fourth, central nervous system leukemia: Table 1 has a meningeal infiltration, can affect the circulation of cerebrospinal fluid, resulting in increased intracranial pressure, patients with headache, nausea, vomiting, blurred vision, papilledema, abductor nerve paralysis and other phenomena. 2 Cranial nerve palsy is mainly the infiltration of nerve roots, especially through the third and seventh pairs of cranial nerve involvement at the cranial nerve hole. 3 The spinal cord is infiltrated by leukemia cells and is characterized by progressive paraplegia. 4 Infiltration of vascular endothelium and stasis of leukemia cells, secondary hemorrhage, clinical manifestations of cerebrovascular accidents. Auxiliary examination 1, blood leukocyte changes are the characteristics of this disease. The total number of white blood cells can be higher than 100 x 109 / L, and can also be lower than 1 × 109 / L. About 30% is below 5×109/L. The proportion of immature lymphocytes in the classification may vary depending on the diagnosis of morning and evening and typing. Most of them are over 20%, and there are also more than 90%. A small number of patients do not have immature lymphocytes in the early stage, and lymphocytes are mainly classified in this type of leukemia. Anemia is generally positive pigmentation of positive cells. However, in severe cases, the MCV may increase, possibly due to bone marrow erythropoiesis. Reticulocytes are normal or low. The degree of anemia is different, the incidence is acute, and the degree of anemia is mild. Platelets are mostly reduced, about 25% in the normal range. Read more...