Scientists from the U.S. found out that the cause of marrow failure in acute myeloid leukemia is not a physical filling of the abnormal cells, and increasing concentrations of interleukin-6. After mice with leukemia were injected with interleukin 6 antibody, the concentration of hemoglobin and myeloid progenitor cells in their blood increased, also increased the lifespan of animals. Article published in the journal Science Translational Medicine.
Acute myeloid leukemia — a malignant tumor in which bone marrow or peripheral blood accumulate pathologic myeloid progenitor cells. The result is broken the bone marrow, decreases the number of red blood cells, platelets, and normal white blood cells. Patients who achieve remission hematopoiesis is restored, and therefore, the mechanisms of its occurrence reversible.
It is considered that the bone marrow failure occurs as a result of his physical filling of the abnormal cells. But its symptoms, there are patients who do not have many leukemic cells. So, there are other possible mechanisms of disruption of the bone marrow. It is known that leukemic cells absorb thrombopoetin and secrete mediators of inflammation that interferes with the process of hematopoiesis.
Scientists from Stanford University under the leadership of Tian Zhang (Zhang Tian) analyzed data on the number of blast (immature) forms of leukocytes in the blood of 293 patients with acute myeloid leukemia and to check for a correlation of this parameter with the number of blood cells.
Then leukemic human cells was transplanted into mice and followed the development of cytopenia (shortage of blood cells). Mice were spleen removed, as preliminary studies showed that it compensates for the failure of the bone marrow, activating the blood.
The researchers found no correlation between the number of blast cells in bone marrow and cytopenia — consequently, the physical filling of the bone marrow leukemic cells did not violate the blood. In mice without spleen, which transplanted immature abnormal white blood cells, developed cytopenia, but she also was not associated with overflow of the bone marrow. The number of hematopoietic stem cells and precursors in these animals was reduced (p < 0.001), but the number of proerythroblasts (very early stage of development of red blood cells) was not different from control. The authors suggested that leukemia inhibits the differentiation of myeloid cells at this stage.
To find out what factors leukemic cells affect the differentiation of bone marrow cells, the authors performed RNA-sequencing of blast cells of patients with acute myeloid leukemia. At the same time conducted multiplex analysis of proteins in the secret leikemicakih cells and in the bone marrow. In all three analyses found increased concentration of interleukin 6 (IL-6). Mice that transplanted leukemic human cells, introduced antibodies to IL-6. In two weeks after that animal conentrate hemoglobin and myeloid progenitor cells (p < 0.01) in the blood was increased compared to control, and life expectancy increased.