acute heterozygous leukemia
Introduction
Introduction to acute heterozygous leukemia Acute hybrid leukemia (HAL), also known as acute mixed leukemia (acute mixeded leukemia), is an acute leukemia in which the myeloid cell line and the lymphocyte line are involved together and reach a certain integral. This disease is different from acute myeloid leukemia (MYALL) expressed by myeloid antigen and acute myeloid leukemia (LYAML) expressed by lymphoid antigen. It is a rare acute leukemia with unique clinical and biological characteristics. Recently, with the continuous development of immunolabeling and genetics technology, its incidence rate has increased, accounting for 3% to 20% of acute leukemia. The clinical manifestations of the disease are anemia, infection, bleeding and infiltration, the treatment is poor, and the prognosis is poor. basic knowledge The proportion of illness: 0.001% Susceptible people: no specific population Mode of infection: non-infectious Complications: central nervous system leukemia intracranial hemorrhage
Cause
Acute heterozygous leukemia
First, the cause of the disease
The exact cause of human leukemia has not been known so far, and many factors are thought to be related to the occurrence of leukemia. The virus may be the main factor, in addition to ionizing radiation, chemical poisons or drugs, genetic factors.
1, the virus
Leukemia virus has been isolated from spontaneous leukemia tissues of chickens, mice, cats, cattle and gibbons. It is a retrovirus and is mostly C-type under electron microscope. The etiology of human leukemia has been studied. Decades of history, but so far only adult T-cell leukemia has been caused by viruses. In 1976, Japans Gao Yueqing first reported adult T-cell leukemia or lymphoma (ATL), and later epidemiological investigations were found in southwestern Japan, the Caribbean. The sea area and Central Africa are high-risk areas. In 1980, ATL-related antigens were found in ATL cell lines, and virus particles were found under electron microscope. Gallo of the United States and Rizhao Reif of Japan isolated C from patient cultured cell lines. The reverse-transcribed RNA viruses, named HTLV-I and ATLV, were confirmed to be consistent, which is a significant contribution to the etiology of human leukemia virus. The high-incidence area of ATL is also a high-risk area for HTLV-I infection, HTLV- I is infectious and can be transmitted through mother-to-child transmission of milk, through sexual intercourse and transfusion, other viruses such as HTLV-II and hairy cell leukemia, Epstein-Barr virus and ALL-L3 subfamily The relationship has not been entirely sure, other types of leukemia is still unable to confirm the virus etiology is not contagious.
2. Ionizing radiation
Ionizing radiation has leukemia-like effects. Its effect is related to the size of the radiation dose and the irradiation site. One large dose or multiple small doses can cause leukemia. Whole body irradiation, especially bone marrow exposure, can cause bone marrow suppression and immunosuppression. The rupture and distortion of chromosomes can still be observed for several months. The number of leukemias in survivors in Hiroshima and Nagasaki in Japan in 1945 was 30 times and 17 times higher than that in unirradiated areas. Radiation therapy for ankylosing spondylitis and 32P treatment The incidence of leukemia and leukemia was higher than that of the control group. According to the survey from 1950 to 1980 in China, the incidence of leukemia in clinical X-ray workers was 9, 61/100,000 (standardized rate was 9, 67/100,000), while others The medical staff is 2, 74/100,000 (standardization rate 2, 77/100,000), and radiation can induce acute non-lymphocytic leukemia (ANLL), acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML), and There is often a period of myelosuppression before the onset, and the incubation period is 2 to 16 years. There is no exact basis for whether the diagnostic irradiation will cause leukemia, but the intrauterine irradiation of pregnant women can increase the whiteness of the baby after birth. The risk of blood disease.
3. Chemical substances
The effect of benzene on leukemia is relatively positive. Benzene acute leukemia is mainly composed of acute granules and erythroleukemia. Benzyl-induced chronic leukemia is mainly CML. Alkylation agents and cytotoxic drugs can also cause secondary leukemia. Most of the secondary leukemias are The malignant tumors that occur in the original lymphatic system and are prone to immunodeficiency occur after long-term alkylating agent treatment. The interval between the two is 8 to 8 years. The secondary leukemia caused by chemotherapy is mainly ANLL, and there is often one before the onset. In the hemopenia phase, in recent years, there have been reports of nearly 100 cases of secondary leukemia caused by bis-morpholine in China. This drug is used to treat psoriasis. It is a very strong chromosomal aberration substance. After taking B-morpholine 1~ Leukemia occurred in 7 years.
4, genetic factors
The incidence of certain leukemias is related to genetic factors. Single-oval twins such as one person suffer from leukemia, another person has a 20% chance of developing leukemia, familial leukemia accounts for 0.7% of leukemia cases, occasionally congenital leukemia, and some hereditary diseases often With high incidence of leukemia, including Down, Bloom, Klinefelter, Fanconi and Wiskott-Aldrich syndrome, such as Down syndrome, the incidence of acute leukemia is 20 times higher than the general population, most of the above hereditary diseases have chromosomal aberrations and fractures. But most leukemias are not hereditary diseases.
Second, the pathogenesis
Based on previous research data, the difference from the pathogenesis of AML or ALL is:
1. It is caused by malignant transformation of early hematopoietic cells. Because of hematopoietic stem and high expression of progenitor cell marker antigen CD34 in this disease, some patients have TdT due to myeloid leukemia cells, a nucleus derived from B, T and leukemia lymphocytes. Glycosidases indicate that patients may be involved in pluripotent stem cell involvement with early differentiation-associated antigens.
2. The myeloid or lymphoid series of transformation occurs due to abnormalities in cell differentiation due to certain internal or external factors.
Prevention
Acute heterozygous leukemia prevention
There is no effective preventive measure for this disease. Early detection and early diagnosis are the key to the prevention and treatment of this disease.
Complication
Acute heterozygous leukemia complications Complications, central nervous system, leukemia, intracranial hemorrhage
1, infection, fever is a common complication: lung infections, skin, mucosal infections, etc. can occur.
2, concurrent with central nervous system leukemia: manifested as increased intracranial pressure, intracranial hemorrhage, brain parenchymal compression and cranial nerve palsy.
3, concurrent testicular leukemia: can be expressed as painless swelling, local hardening, can be nodular, scrotal skin color changes.
4, this type of leukemia increased white blood cells, easy to merge with high cell syndrome.
Symptom
Symptoms of acute heterozygous leukemia Common symptoms Lymph node enlargement Hepatosplenomegaly Anemia is prone to bruises and increased intracranial pressure in the lungs
The disease can occur in all age groups, with common clinical features of leukemia such as anemia, hemorrhage, infection and infiltration, but the following performance is more prominent than AML or ALL:
1. There are more white blood cells in the onset, and high white blood cell syndrome is easier to see;
2, extramedullary infiltration performance is obvious, such as testis, central nervous system involvement, liver, spleen, lymph nodes are more common;
3, a variety of standard treatment options are invalid, high recurrence rate, poor efficacy.
Examine
Examination of acute heterozygous leukemia
1. Peripheral blood
Hemoglobin decreased significantly, mostly moderate to severe, and white blood cell hyperplasia (WBC>10×109/L) was more common. Most patients showed thrombocytopenia on the onset. Blood smears showed more uniform leukemia cells, similar to AML or ALL. And naive cell morphological characteristics: leukemia cells may also be heterogeneous, that is, granulocyte-like and lymphocyte-like primitive and immature cells exist in the peripheral blood field.
2, bone marrow and chemical staining characteristics
According to morphological and cytochemical staining, the disease is often diagnosed as AML or ALL. Eighteen patients with HAL have been reported in the literature. According to the FAB classification criteria, 9 of them were diagnosed as AML (M1, 1 case; M2, 4 cases; M4, 1 case; M5, 3 cases), the other 9 cases were diagnosed as ALL (L1, 3 cases and L2, 6 cases), bone marrow cell morphology found that leukemia cells can be homogenous or heterogeneous, showing myeloid and Or) lymph node characteristics, Auers bodies can be seen in some cases, 5 cases of HAL patients have been reported in China, the chemical staining characteristics are: 4 cases of POX positive, 1 case negative; 5 cases of PAS have different degrees of positive; 4 cases of NAS-D -AE positive, 1 case was inhibited after adding NaF, and 4 cases were simultaneously investigated for NAS-D-CE, and only 1 case was positive.
3. Cellular immunolabeling
Immunohistochemistry and flow cytometry can be used. Up to now, flow cytometry has been widely used in clinical tests to detect HAL immunomarkers. For example, T lymphocytes are most specific to CD3, especially cytoplasmic CyCD3 is expressed in the membrane (MCD3). CyCD22 is considered to be the most sensitive marker of B-ALL. No expression of CyCD22 is observed in AML. Recently, CD20 is one of the more reliable expressions of B-ALL, and anti-MPO is one of the most reliable markers of myeloid. In addition, CD13 and CD33 are also first-line diagnostic markers for granulocyte cell lines.
4. Cytogenetics
The cytogenetic changes of this disease are more complicated, and the more common chromosomal changes are: t(9;22),-5/5q-, inv(16),11q23,t(8;21), etc., retrospective analysis by Cuneo et al. HAL chromosomal variation data, found that t (15; 17), inv (16) and -5/5q- and / or -7 / 7g - common in TML containing T lymphocyte characteristics, T (8; 21) (q22; Q22), t(q;22) and 11q23 rearrangement are more common in AML with B lymphocyte characteristics, while t(9;22), tllq23 and 14q32 (no immunoglobulin heavy chain gene rearrangement) are found in myeloid The ALL of the logo.
According to clinical manifestations, symptoms, signs, chest X-ray, CT, MRI, B-ultrasound, electrocardiogram, etc.
Diagnosis
Diagnosis and differentiation of acute heterozygous leukemia
Diagnostic points
1, diagnostic criteria
In 1987, Gale and Ben-Bassat proposed diagnostic criteria for HAL, mainly using techniques such as cytochemistry, morphology (Auers bodies), immunology and immunoglobulin heavy chain gene rearrangement and T cell receptor gene rearrangement. At home and abroad, the HAL diagnostic criteria (Table 2) established by the European group of immunological characterization of leukemia (EGIL) in 1994 are used. The diagnosis of double phenotype must have a cell expressing both myeloid and lymphoid markers. .
It should be noted that only aberrant expression of individual, secondary, non-series related antigens can not diagnose HAL, but should be diagnosed with lymphoid cell-associated antigen-positive acute myeloid leukemia (Ly AML) or with myeloid-associated antigen Positive acute lymphoblastic leukemia (MY ALL).
2, HAL classification
The HAL classification has not been unified, and can be divided into 4 different types according to the source of the affected cells and the immune expression:
(1) Biphentypic: The leukemia cells are more uniform, and the leukemia cells of the patient simultaneously express the characteristics of the myeloid cell line and the lymphocyte lineage, that is, the single leukemia cells simultaneously express the histochemical and immunological markers of the myeloid and lymphocyte lines, and the cells Count 10%.
(2) Double-type (biclonic) also known as bilineal type (bilineal): leukemia cells are heterogeneous, some of them express myeloid characteristics, and the other part express lymphoid characteristics. The second type of cells are derived from their respective Pluripotent stem cells need to be limited only when the second type of cells coexist, or occur in succession within half a year.
(3) bilined: similar to the double clonal type, but the two types of cells are derived from the same pluripotent stem cell.
(4) series transition type (1ineal switch): refers to leukemia cells change from one phenotype to another (the course of disease changes more than half a year), leukemia chemotherapy may lead to a series of transformation (such as lymphoid system myeloid system, Or one of the most important factors of the myeloid system.
It is mainly identified based on cellular immunological markers and genotyping.
