adult T-cell leukemia
Introduction
Introduction to adult T cell leukemia Adult T-cellleukemia (ATL) is a special type of lymphatic system malignant clonal proliferative disease that is directly related to human T-cell leukemia virus I (HTLV-I) infection and occurs in adults. Blood lymphocytes can also invade the bone marrow. basic knowledge The proportion of illness: 0.004% Susceptible people: no specific people Mode of infection: non-infectious Complications: respiratory failure
Cause
The cause of adult T cell leukemia
(1) Causes of the disease
The occurrence of ATL is associated with human T-cell leukemia virus type I (HTV-I) infection. The patient's serum HTLV-I is positive. The high-incidence area is the southern part of Kyushi Island, Japan. Here, 10% to 15% of residents are positive for HTLV-I antibody. The incidence rate in other places is very low, and it is unclear how to link the incidence of high-incidence areas in Japan with other areas.
Studies have shown that host susceptibility and/or common environmental conditions are associated with HTLV-I infection. The positive rate of HTLV-I antibody in family members is 3-4 times that of unrelated normal population, and can be separated in serum of patients with positive antibody and clinically normal. Out of the HTLV-I virus.
(two) pathogenesis
The long-term incubation period after HTLV-I infection may eventually lead to a small number of people suffering from ATL. This itself illustrates the complexity of ATL. So far, the pathogenesis of ATL has not been finally elucidated. Many data suggest that the pathogenesis of ATL may be related to the following mechanisms.
1. Regulatory protein Tax At the end of the HTLV-I provirus, there is a long terminal repeat (LTRs) containing regulatory portions of the virus, including the promoter sequence, by U3, R and U5 (unique 3' end, repeat, Composed of a 5'-end sequence, the main function of Tax is to transactivate the transcriptional function of HTLV-I through the 5'-LTR sequence to regulate viral replication, which activates transcription of viral and cellular genes through at least two different host transcription factor pathways. Involved in CAMP response component protein, activation transcription factor (ATF) and transcription factor NF/B/C-Rel family, respectively, Tax may have the following effects in the pathogenesis of ATL: 1 activate IL-2 promoter and IL-2R subunit, Stimulate T cell autocrine growth, even initiate T cell immortalization, and finally to the occurrence of ATL: including IL-2 and IL-2Ra, c-fos, c-jun and parathyroid hormone-related protein (PTHrP), ATL The release of these cytokines by cells can cause a series of pathological manifestations: IL-2 and IL-2Ra can lead to the activation and proliferation of T cells, and achieve self-regulation; PTHrP can stimulate osteoclasts, causing patients to show hypercalcemia Disease; c-fos gene may be involved in T Proliferation, 2Tax can accelerate the progression of G1 phase in the cell proliferation cycle and promote its entry into S phase. The cell proliferation cycle of Tax expressing is shortened and the cell growth kinetics is increased, which may be related to the occurrence of HIIIV-I related diseases; 3Tax Mediated changes in NF-B activity may have a role in tumorigenesis.
2. The immune function of HTLV-I is reduced. Tax can increase the expression level of activated transforming factor 1 (TGF1), while the latter can inhibit human cell and humoral immunity. After HTLV-I is infected, it can be encoded by virus. The new HLA-I and HLA-II antigenic determinants lead to immune dysfunction, and the body's defense ability declines, creating conditions for the occurrence and development of tumors.
3. Oncogene activation and anti-oncogene inactivation Although HTLV-I does not encode oncogenes, cis-activation mechanisms may still exist. For example, Tax activates c-fos gene, indicating that high-efficiency transactivation protein Tax may be activated. Related to malignant transformation.
Prevention
Adult T cell leukemia prevention
And it should be noted that when eating fruit, it must be washed or peeled, so as to avoid the residual components of pesticides, thus aggravating the condition. It is also necessary to remind that the food and food utensils consumed by the patient should be kept clean from time to time to avoid infection.
Complication
Adult T cell leukemia complications Complications, respiratory failure
Infection is the most common complication and can be secondary to bacterial, fungal and Pneumocystis carinii infections.
Symptom
Adult T-cell leukemia symptoms Common symptoms Ascites skin infiltration hypercalcemia fatigue leukemia cell infiltration expression indifference pleural effusion peritoneal effusion hepatosplenomegaly skin involvement
ATL patients have a variety of clinical manifestations, which can be expressed as a leukemia-like acute type, a lymphoma-proliferating lymphoma type, a chronic prognosis with a good prognosis (insidious type).
Almost all patients have lymphadenopathy, many patients have extensive lymphadenopathy, most have retroperitoneal lymphadenopathy, but mediastinal mass is rare, bone marrow often has leukemia cells infiltration, other common sites of involvement are lung, liver, skin , the gastrointestinal tract and the central nervous system.
Approximately 2/3 of patients may develop skin involvement, and most patients with skin infiltration may have focal ATL cell infiltration or Pautrier microabscesses.
Main clinical manifestations of each type
1. Acute type: The median age of the patient is 40 years old. The typical manifestation is: the onset is very urgent, mainly the rapid development of skin damage, hypercalcemia, or both, and the skin damage is diverse, such as scattered distribution. Tumor mass, fused small nodules, plaques, papules, non-specific erythema, etc., hypercalcemia patients often manifest as fatigue, indifferent expression, mental confusion, polyuria, polydipsia.
2. Chronic type: may have lymphadenopathy, hepatosplenomegaly, skin and lung infiltration, no hypercalcemia, no central nervous system, bone, gastrointestinal infiltration, no ascites and pleural effusion.
3. Lymphoma type: lymph node histology proved to be lymphadenopathy, no leukemia cell infiltration.
4. Smoke type: skin damage is characterized by erythema, papules, nodules, pulmonary infiltration, general no hypercalcemia, lymphadenopathy, hepatosplenomegaly and bone marrow infiltration are mild; no central nervous system System infiltration.
Examine
Adult T cell leukemia examination
1. Peripheral blood: Unlike other acute leukemias, ATL patients generally have no anemia and thrombocytopenia, even those with anemia and thrombocytopenia, the degree is mild, severe anemia and thrombocytopenia are rare, white blood cell count is often increased, especially Found in acute and chronic patients, lymphocytes accounted for 10% to 90%, lymphocytosis is also mainly seen in acute and chronic ATL patients.
2. Bone marrow: lymphocytes can be less than 30%, but also more than 60%. Polymorphonuclear lymphocytes are one of the characteristics of this disease, accounting for more than 10% of peripheral blood, and PAS-positive for cell chemistry. Acidic phosphoric acid Enzyme positive, TdT negative, peroxidase negative.
3. Immunophenotype: The most common phenotype is CD4 CD8-, but some patients show CD4 CD8-, CD4-CD8 or CD4 CD8- phenotypes, and ATL cells are commonly expressed as CD2, CD3, CD4, CD8-, CD25.
4. Cytogenetics: ATL has no single prominent chromosomal translocation, but 28% affects q32 on chromosome 14, 15% affects q11, chromosome 7 triploid, 6q-, 13q-, 14q+, 3p+ are also more common .
5. Virological examination: anti-HTLV-I antibody can be detected by enzyme-labeled immunoassay or indirect immunofluorescence assay; RT-PCR method can be used to detect HTLV-I viral RNA expression in tumor cells, especially HTLV proviral DNA positive for this disease The diagnosis is of great significance; using PCR technology to detect the pre-viral load of HTLV-I is beneficial to the early evaluation of ATL tumor burden.
6. Biochemical examination: hypercalcemia, GOT, GPT, LDH, bilirubin, elevated alkaline phosphatase.
7. X-ray: chest radiographs can show diffuse infiltration of both lungs, and osteophyte X-ray plain films often have osteolytic lesions.
8. B-ultrasound: superficial lymphadenopathy, retroperitoneal lymphadenopathy, hepatosplenomegaly can be prompted.
9. Pathological examination: lymph node, skin biopsy can be seen ATL cell infiltration.
Diagnosis
Diagnosis and diagnosis of adult T cell leukemia
Diagnostic criteria
1. Domestic Diagnostic Criteria (ATL Collaboration Conference of Some Provinces and Cities in 1984)
(1) Clinical manifestations of leukemia: 1 onset in adults; 2 with superficial lymphadenopathy, no mediastinal or thymic tumors.
(2) Laboratory examination: peripheral blood leukocytes often increase, polymorphonuclear lymphocytes (flower cells) account for more than 10%; T cell type, with mature T cell surface markers; serum anti-HTLV-I antibody positive.
2. ATL foreign diagnostic criteria (Schimoyama Metal, 1991)
(1) Histological and/or cytochemical evidence of lymphocytic leukemia with T cell surface antigen (mainly CD2, CD3, CD4).
(2) Peripheral blood must have abnormal T lymphocytes, including typical adult T lymphocytic leukemia cells (also known as flower cells and small but mature T cells, with sagged depressions or lobulated nuclei in the nucleus).
(3) Anti-human T lymphocytic leukemia virus type I (HTLV-I) antibody is positive.
3. Diagnostic criteria for ATL subtypes (Gessainetal, 1992)
(1) Smoke type:
1 peripheral blood abnormal T cells 5%.
2 The total number of lymphocytes is normal.
3 no hypercalcemia, LDH 1.5 × normal value.
4 no lymphadenopathy; no liver, spleen, CNS, bone, gastrointestinal involvement.
5 no peritoneal effusion or pleural effusion.
6 may have skin and lung damage.
7 If abnormal T cells <5%, there should be histologically confirmed skin and lung damage.
(2) Chronic type:
1 The absolute number of lymphocytes increased ( 4 × 109 / L) with T cells > 3.5 × 109 / L, including abnormal T cells and occasional petal-shaped cells.
2 no hypercalcemia, LDH 2 × normal value.
3 no CNS, bone, gastrointestinal involvement, no pleural effusion or ascites.
4 may have lymph nodes and spleen, liver, lung, skin involvement.
(3) Lymphoma type:
1 no lymphocyte increase, with abnormal lymphocytes 1%.
2 histologically positive lymph node lesions.
(4) Acute type:
1 Except for the above-mentioned type 3 ATL patients, often have leukemia and lymphadenopathy.
2 Histological and (or cytologically confirmed T lymphocyte tumors).
3 In addition to lymphoma ATL, peripheral blood should have abnormal T lymphocytes, including typical "petal" cells and small mature T lymphocytes with notched and lobulated nuclei.
4LTHV-1 antibody is positive.
Differential diagnosis
1. Mycosis fungoides/sezary syndrome Mycosis fungoides/sezary syndrome (MF/SS) is a mature and mature T cell malignant disease, similar to ATL, both of which have skin infiltration lesions in the new WHO. In the classification of leukemia and lymphoma, both are classified as mature (peripheral) T cell tumors, the difference is:
1ATL leukemia cells generally do not infiltrate the epidermis;
2ATL cells differ from typical sezary cells in that the nucleus of the former is mostly lobular nucleus;
3ATL often involves bone marrow;
The 4ATL clinical process is more aggressive than MF/SS.
2. T-cell chronic lymphocytic leukemia (T-CLL) T-cell chronic lymphocytic leukemia (T-CLL) is also a mature T-cell malignant tumor, which differs from ATL in that:
1ATL cell morphology is different from T-CLL cell morphology;
2ATL clinical progress is invasive;
3ATL patients were positive for HTLV-I antibodies, while T-CLL was negative.
3. Skin T-cell lymphoma has many chronic pre-existing conditions, and the slower onset is not related to HTLV-1 infection.
