juvenile myelomonocytic leukemia
Introduction
Introduction to juvenile granulocyte-monocytic leukemia Juvenile myelomonocyticleukemia (JMML) is a rare clonal hematopoietic stem cell hyperplasia that occurs mostly in infancy. basic knowledge Sickness ratio: 0.0001% Susceptible people: children Mode of infection: non-infectious Complications: bronchitis, eczema
Cause
Juvenile granulocyte-monocytic leukemia
(1) Causes of the disease
JMML originates from pluripotent hematopoietic stem cells, so it can cause erythroid hyperplasia, abnormal platelet count and quantity, and abnormal lymphocyte function. Unlike adult type, its abnormal proliferation mainly occurs in granulocyte system, and in vitro stem cell culture mainly forms CFU-GM. The chromosome examination is mostly normal, and -7, 8 (8 trisomy) or 21 (trisomy 21) can be seen individually, 6% to 20% have monomer 7 and t(1; 13), t(7; 11 ), t(7;20), 13 (13 trisomy), JMML is closely related to multiple neurofibromatosis type I (NF1), and then people are concerned that NF1 is an autosomal dominant genetic disease, NF1 children are obvious Increased risk of developing malignant myeloid leukemia, including granulocyte monocytic leukemia, acute myeloid leukemia, NF1 gene located at 17q21.2, cloned in 1990, encoding neurofibromin, about 15% of JMML Children with NF1, 15% without NF1 evidence and NF1 gene mutation, the loss of NF1 gene activates the intracellular Ras signaling pathway, which leads to the development of leukemia in children with NF1.
The etiology of JMML is unclear. More than 20% of patients have abnormal chromosome 7 such as monomer 7, and other chromosomal abnormalities include t(1;13), t(7;12), t(7;20), 13, 21, 8, etc., but the correlation between chromosomal abnormalities and the pathogenesis of JMML is still unclear.
(two) pathogenesis
At the level of molecular biology, 15% to 30% of patients in JMML have a point mutation in the Ras gene. The Ras gene is a proto-oncogene. The mutation of Ras gene activates the Ras signaling pathway and is a mechanism of tumorigenesis. In addition, about 15% of children with JMML have multiple neurofibromatosis type I (NF1), 15% have no NF1 evidence and have NF1 gene mutation, and NF1 is an autosomal dominant genetic disease. Increased risk of malignant myeloid diseases, including granulocyte monocytic leukemia and acute myeloid leukemia, NF1 gene located at 17q11.2, encoding Ras-GPT enzyme active protein, plays a role in GM-CSF signaling pathway, NF1 gene is not As a tumor suppressor gene in mature myeloid cells, negatively regulates hematopoietic growth by affecting Ras-GPT, and the loss of NF1 gene activates Ras signaling pathway in cells, leading to the development of leukemia, abnormal clone formation and Ras pathway in children with NF1. The dysregulation is two different stages of leukemia formation. Ras pathway activation is a prerequisite for JMML formation. About 50% of JMML has evidence of activation of Ras signaling pathway by Ras or NF1 mutation. However, 50% of J is still present. No abnormalities in the NF1/Ras pathway have been observed in MML patients. The pathogenesis of these patients and the relationship with the Ras pathway are still uncertain. The p53 gene is a tumor suppressor gene. It has been reported that the 31st exon of the NF1 gene has a germline in the diagnosis of JMML. Mutation, loss of exon 6 of the wild-type p53 allele during disease progression, and no loss of NF1 allele, indicating that NF1 and p53 are associated in JMML tumor formation and progression.
JMML is also a disease from pluripotent hematopoietic stem cells, but its molecular biological abnormalities are significantly different from adult MPD. JMML cells cultured in vitro are highly sensitive to GM-CSF, but this phenomenon is not observed in other growth factors such as IL-3. Without exogenous hematopoietic factors, the granulocyte-derived progenitor cells of JMML patients can grow spontaneously in large numbers. This self-generating length is not due to the increase of GM-CSF concentration, but due to the increased sensitivity of progenitor cells to GM-CSF. As a result, this spontaneous clonal growth is rarely seen in other MPD and Ph CML and normal humans. Therefore, cell culture granule mononuclear cloning plays an important role in the diagnosis of JMML. JMML cells maintain monoclonal properties through long-term culture, while Ph CML Cells form polyclonal in the same culture system.
Prevention
Juvenile granulocyte-monocytic leukemia prevention
1. Avoid contact with harmful factors: pregnant women and children should avoid exposure to harmful chemicals, ionizing radiation and other factors that cause leukemia. When exposed to poisons or radioactive materials, various protective measures should be strengthened; avoid environmental pollution, especially indoor environmental pollution; Pay attention to the rational use of drugs, use cytotoxic drugs with caution.
2. Vigorously carry out prevention and treatment of various infectious diseases, especially viral infectious diseases, and do a good job of vaccination.
3. Do a good job in eugenics to prevent certain congenital diseases, such as 21-trisomy, Fanconi anemia, etc.
Complication
Juvenile granulocyte-monocytic leukemia complications Complications, bronchitis, eczema
Bronchitis, pulmonary infection; liver, spleen, lymphadenopathy; eczema-like rash, suppurative rash; bleeding due to thrombocytopenia.
Symptom
Juvenile granulocyte-monocytic leukemia symptoms common symptoms lymphadenopathy thrombocytopenia bloating papules persistent fever pulmonary infection
95% of the children were younger than 4 years old at the time of diagnosis, 60% of them occurred before the age of 2, more men than women, and males and females were 1.4 to 2.5:1.
Onset can be urgent or slow, often with respiratory symptoms as the main complaint, the most common manifestations are fever, discomfort, cough, bloating, tonsillitis, bronchitis, lung infections, the most important is the performance of myeloproliferative diseases, liver , spleen, swollen lymph nodes, skin damage is a common and important feature, seen in more than half of the children, manifested as facial rash or eczema-like rash, even purulent rash, xanthomas, milk coffee spots, due to platelets It is not uncommon to reduce and then send blood, and it does not respond to hormone therapy.
Examine
Examination of juvenile granulocyte-monocytic leukemia
Blood picture
Hb is mildly moderately reduced, Plt is reduced, half is below 50×109/L, leukocytosis is increased, 2/3 children are below 50×109/L, and a few children (<10%) are greater than 100×109/L. The number of nucleated cells increases, and the granulocytes and erythrocytes appear in the peripheral blood. The eosinophils and basophils may increase but are not as obvious as Ph1CML.
2. Bone marrow
Granuloid hyperplasia, visible pathological hematopoiesis, erythroid pathogenic hematopoietic rare, megakaryocytes decreased, mononuclear system accounted for 5% to 10%, bone marrow pathology in some children with fibrous hyperplasia, but less common than Ph1CML.
3.JMML
HbF increased in children, 2/3 children had HbF>10%, HbA2 decreased, immunoglobulin increased in polyclonal, serum lysozyme increased, neutrophil alkaline phosphatase decreased, normal or increased, and could not provide diagnosis in accordance with.
4. Cell culture
Most experimental studies have shown that in the absence of exogenous hematopoietic factors, granulocyte-derived progenitor cells (CFU-GM) can grow spontaneously in large numbers, while normal hematopoietic progenitor cells grow inhibited, and this self-generating length appears as a granule-giant The phagocyte colony-stimulating factor (GM-CSF) is selective, and the anti-GM-CSF antibody can selectively inhibit the growth of JMML clones, while other growth factor antibodies can not inhibit the clonal growth, so the cell culture GM clone spontaneous growth to JMML Diagnosis plays an important role.
B super visible liver, splenomegaly; chest radiograph visible bronchial or lung inflammation shadow.
Diagnosis
Diagnosis and identification of juvenile granulocyte-monocytic leukemia
diagnosis
In 1997, the International JMML Collaboration Group developed standards: this standard is currently widely recognized.
Clinical features
1 hepatosplenomegaly;
2 lymph nodes;
3 pale;
4 fever;
5 skin damage.
2. Minimum laboratory standards (satisfying all 3 conditions)
(1) Ph- or bcr/abl-.
(2) Peripheral blood mononuclear cell count > 1 × 10 9 /L.
(3) Bone marrow blast cells <20%.
3. Standards for clarifying diagnostic requirements
(1) HbF increases with age.
(2) Peripheral blood smears can be seen in myeloid naive cells.
(3) Leukocytes > 10 × 109 / L.
(4) Clonal abnormalities (including monomer 7).
(5) Cultured myeloid cells in vitro are highly sensitive to GM-CSF.
Differential diagnosis
1. Infant-stage leukemia reaction: There may be liver splenomegaly, thrombocytopenia, occasional mid-young granules and nucleated red blood cells in the peripheral blood, but there are often chronic infections, no increase in monocytes and a significant increase in HbF.
2. Cytomegalovirus and Epstein-Barr virus infection: may have fever, hepatosplenic lymph node enlargement, leukocytosis, thrombocytopenia, but the bone marrow often shows hyperplasia, megakaryocytes do not decrease, no obvious mononuclear cells increase and HbF increase significantly, virus The test was positive.
3. Langerhans histiocytosis: can be expressed as leukocytosis, mononuclear cells, hepatosplenomegaly, skin damage, and the characteristic identification of JMML is the majority of children with bone damage and in the bone marrow, spleen S-100 Langerhans cells were found in tissues such as skin.
4. Adult CML identification.
