acute promyelocytic leukemia
Introduction
Introduction to acute promyelocytic leukemia Acute promyelocytic leukemia (APL) is a special type of acute myeloid leukemia (AML), which is classified as acute myeloid leukemia M3 by the FAB collaborative group. In recent years, with the continuous improvement of the understanding of the characteristics of APL cell biology and the improvement of treatment methods, the treatment results and prognosis have been greatly improved, and early mortality has decreased significantly. Acute promyelocytic leukemia is not uncommon in clinical practice. Patients are often younger. The median age is 30-38 years old, and those under 10 years old are rare. According to China's complete statistics, the incidence of M3 is higher than that of western countries. , accounting for 18.7% of AML in the same period. In some areas, such as the Northeast Oilfield, the incidence of M3 may be as high as 20% to 30% or even higher in AML. Foreign data show that the incidence of Latino ethnicity in Europe, Central and South America is higher. APL accounts for about 10% to 15% of adult primary AML, but there may be differences in age and ethnicity. basic knowledge The proportion of illness: 0.035% Susceptible people: no special people Mode of infection: non-infectious Complications: sepsis shock
Cause
Acute promyelocytic leukemia
Cause (60%):
The etiology of primary APL is not fully understood at present. Secondary patients are often seen in cancer patients with chemotherapy and/or radiotherapy. There are also reports of APL caused by alkylating agents and topoisomerase II inhibitors. Secondary APL The prognosis is good, and its response to treatment and long-term survival rate are similar to those of the original, but the AML associated with chemotherapy is significantly different.
Pathogenesis (30%):
APL is a type of leukemia that responds well to the induction of differentiation therapy, which is related to the change of chromatin induced by the retinoic acid receptor (RAR) fusion protein expressed in APL cells. The five chromosomes of APL have been reported to be easy. Both of them involve the RAR gene on chromosome 17, which is 39398 bp in length and contains 9 exons and 8 introns. The t(15;17) translocation is found in most APL patients, retinoic acid receptors. The alpha gene forms a PML-RAR fusion gene with the promyelocytic leukemia (PML) gene of chromosome 15, and the protein encoded by the fusion gene has a function different from that of the wild-type retinoic acid receptor encoded by the normal RAR allele, RAR. The gene is located in the long arm 2l region of chromosome 17, and its function is the nuclear hormone receptor. The retinoic acid binds to the RAR receptor element, and transcription regulates many genes. PML is a nuclear protein, from the amino terminus to the carboxy terminus, including hydrazine. The acid-rich region, the cystine-rich region required for nucleosome localization, forms the helical loop helix required for homo/dimers, the nuclear localization signal NLS, and the serine-rich proline-rich region. PML is normally located in a scale. For the knot of POD (PML oncogenic domain) (also known as nucleosome, polyprotein nuclear), POD is spotted in the nucleus, the number is 15-20, the function of PML has not been fully elucidated. Recent studies suggest that PML inhibits tumor growth through transcriptional co-activation. PML may also play an important role in a variety of apoptotic pathways. In M3 AML (acute promyelocytic leukemia), RAR on chromosome 17 translocates with PML on chromosome 15, ie The occurrence of t(15;17)(q22;q21), the mutual translocation of PML and RAR causes the following consequences:
1PML-RAR fusion protein inhibits promyelocytic differentiation and maturation by dominant negative inhibition;
2PML delocalizes to form hundreds of fine particles, which are distributed in the nucleus and cytoplasm, which destroys the structure of POD, and the normal inhibition of proliferation and pro-apoptotic function of PML leads to cell proliferation and apoptosis.
3RAR normally binds to the transcriptional co-suppression complex (N-CoR/Sin3a/HDAC-1) (N-CoR=nuclear receptor co-inhibitor, HDAC=histone deacetylase), in physiological dose A Under the action of acid, RAR can dissociate from the co-suppressor complex and activate transcriptional activation, ie, activate the regulated target gene. PML-RAR can promote the binding of RAR to the co-suppressor complex, inhibit the target gene regulated by RAR, and inhibit the early detection. The young cells differentiate and mature and proliferate, causing M3 type AML. At therapeutic dose, ATRA can degrade PML-RAR. In addition, ATRA can also separate the co-suppressor complex from RAR, thereby recruiting coactivators. Complexes, including CBP/P300, P/CAF, NcoA-1/SRC-1, P/CIF, etc., in which CBF/P300 and P/CAF have strong histone acetylase activity, which makes histone acetylation, After histone acetylation, the function of transcriptional activation of the target gene is restored, and the promyelocytes are differentiated and mature.
1% to 2% of APL has a variant t(11;17)(q23;q21), which fuses the promyelocytic leukemia zinc finger gene (PLZF) on chromosome 11 with the RAR gene located on chromosome 17. The fusion protein of PLZF-RAR and RAR-PLZF was simultaneously expressed in all patients reported so far, suggesting that the pathogenesis of t(11;17)(q23;q21) APL may require the corresponding action of RARot-PLZF fusion protein, t(11; 17) (q23; q21) APL is not sensitive to ATRA, and less common variant chromosomal translocations have t(5;17)(q35;q21) leading to fusion of NPM (nucleophosmin) with RAR gene; t(11;17)( Q13;q21)Generating the NuMA-RAR fusion gene, dup(17)(q21.3-q23) produces the STATSb-RAR fusion gene, the first two translocation patients are sensitive to ATRA, but ATRA is positive for STAT5b-RAR fusion gene invalid.
The leukemia effect of the APL fusion gene has been confirmed in a transgenic animal model, and hCG-PML-RAR transgenic mice expressing PML-RAR under the control of hMRP8 or human cathepsin G microgenes occur about 1 year after birth. APL-like leukemia, and hCG-PLZF-RAR transgenic mice develop chronic myeloid leukemia-like lesions 3 to 12 months after birth, with promyelocytic elevation in the bone marrow, while transgenic genes expressing PLZF-RAR and RAR-PLZF Human-like APL occurs in mice, and NPM-RAR transgenic mice develop typical APL or chronic myeloid leukemia-like lesions 1 year after birth.
Prevention
Acute promyelocytic leukemia prevention
1. Do not touch X-rays and other harmful radiation too much. Personnel engaged in radiation work should do personal protection and strengthen preventive measures. Infants and pregnant women are more sensitive to radiation and vulnerable to injury. Women should avoid exposure to excessive radiation during pregnancy, otherwise the incidence of leukemia in the fetus is higher. However, the occasional, medical x-ray examination, the dose is small, basically does not affect the body.
2. Do not abuse drugs. Care should be taken when using chloramphenicol, cytotoxic anticancer drugs, immunosuppressive drugs, etc., and must be guided by a doctor. Do not use or abuse them for a long time.
3, when choosing food, eat more high-protein, high-fiber, high-calorie foods, eat more fresh fruits and vegetables, taboo to eat greasy, cold, spicy spicy food, the best ratio of meat is 3: 7. Also try to avoid eating too much processed meat, which will increase the risk of leukemia.
4, a medical investigation found that chronic benzene poisoning mainly damages the human hematopoietic system, causing leukocytes and platelet counts to reduce leukemia. Benzene pollution and formaldehyde pollution in the indoor environment caused by decoration and furniture all cause harm to people's health. The use of natural stone and ceramic tiles is the main cause of radioactive cesium contamination in indoor environments. Therefore, be sure to ventilate and dry after the renovation. I bought a fan with clean air, and I also bought a large amount of activated carbon, spider plant, and green radish that can absorb harmful gases such as formaldehyde and benzene. It is best to measure with professional instruments before entering the station.
5, sleeping too late or often plus night shifts will increase the risk of leukemia. The increased incidence of leukemia is related to exposure to light at night. Studies have shown that people who turn on the lights and sleep, or people whose natural sleep patterns are disturbed by artificial light, are more likely to develop cancer than normal people. At night, light can confuse people's circadian rhythms and inhibit the normal secretion of melatonin, which is associated with cancer cell growth. Therefore, people should pay attention to rest and go to bed according to the biological clock, and turn off the lights until they wake up the next morning.
Complication
Acute promyelocytic leukemia complications Complications septic shock
1. Infection is the most common complication
Including bacteria, viruses, fungal infections, mainly manifested as fever, the site of infection is common in the mouth, lungs, skin, severe cases can occur sepsis, infection toxic shock.
2, DIC is the most important complication of APL
The incidence is high, about 60% of patients occur. In recent years, with the application of formic acid and arsenic, the occurrence of DIC has been significantly reduced.
3, in the application of vitamin A acid treatment process will be combined with high white blood cell disease, vitamin A syndrome, can be given hydroxyurea, low-dose Ara-C or reduced AA, DA regimen treatment.
Symptom
Acute promyelocytic leukemia symptoms common symptoms bleeding tendency intravascular coagulation bone pain lymph node enlargement
Clinical manifestations of acute promyelocytic leukemia are associated with normal bone marrow hematopoietic failure, such as anemia, hemorrhage, infection; infiltration-related manifestations of leukemia cells, such as hepatosplenomegaly and lymphadenopathy, bone pain, etc., in addition to these leukemias In addition to general leukemia, bleeding tendency is its main clinical feature. 10% to 20% of patients die of early bleeding, the incidence of disseminated intravascular coagulation (DIC) is high, and DIC occurs in about 60% of patients.
Examine
Examination of acute promyelocytic leukemia
1. Peripheral blood
A typical blood picture shows anemia, changes in the number of white blood cells, and visible immature cells, thrombocytopenia.
2, bone marrow
Promyelocytic hyperplasia with abnormal granules is mainly >30%, most >50%, and the cell morphology is more consistent. The primordial cells have fewer cells in the following stages, and the nucleus morphology is irregular, with internal and external granules, and outer pulp. No particles, there are particles of uneven size in the inner pulp, according to the size of the particles can be divided into:
M3a (coarse particle type): The cytoplasm is filled with coarse azurophilic blue particles, and densely distributed, and the particles can also be covered on the school.
M3b (fine particle type): The aniline blue particles in the cytoplasm are fine and densely distributed.
3, cellular immunological examination
The protein is CD33, 13 (HLA-Dr negative).
4. Cytogenetic examination
Chromosomal abnormalities, t(15;17)(q22;q21).
5, clotting time
3P test, fibrinogen content, plasminogen content and activity, ATPP (activated partial thromboplastin time), PT (prothrombin time).
6, biochemical and electrolyte examination, liver and kidney function examination.
According to the condition, clinical manifestations, symptoms, signs, X-ray, CT, MRI, B-ultrasound, electrocardiogram, etc.
Diagnosis
Diagnosis and differentiation of acute promyelocytic leukemia
Diagnostic criteria
According to the morphological diagnostic criteria of FAB, the diagnosis is based on FAB classification acute promyelocytic leukemia (APL), also known as AML-M3 type. Typical characteristics are:
1. The bone marrow morphology is abnormal promyelocytic proliferation of cytoplasm containing coarse particles and Auer bodies (also with microparticle variants);
2, clinical often have severe bleeding, and easy to combine DIC and fibrinolysis;
3. 90% of patients show specific ectopic t (15; 17);
4, chemotherapy sensitive (chemotherapy resistance rate <5%), to ease long survival, but early mortality is high.
Differential diagnosis
It is mainly identified with other types of leukemia, and its identification points are generally not difficult to identify according to cell morphology, cellular immunological examination, and cytogenetic examination.
