Chronic myeloid leukemia

CML is a chronic myeloproliferative disease caused by a disorder of pluripotent stem cells, both the myeloid and lymphoid hemorrhage series are affected, the predominance is affected by granulopoiesis (often combined with thrombocytopoiesis).

A characteristic feature of cancer cells in CML is presence of thePhiladelphia Ph chromosome 1 translocation of part 9 of the Chromosome – carries protooncogene c-abl) to the 22nd chromosome (bcr gene) – a fusion bcr/abl gene is produced, which can be demonstrated even in cases where the Ph-chromosome cannot be determined (about 10% CML). The proliferation of the pathological clone gradually displaces normal hematic formation and leads to a multiple increase in the total granulocyte mass, the presence of a Ph-chromosome leads to further mutations in the formation of malignant clones with greater proliferation activity (de-differencing of malignant cells) – these new populations gradually replace the original "benign" leukemia clone and eventually completely prevalent – the so-called "benign" leukemia clone. blast reversal (course as with AML with massive blast leaching – more than 30% of monoblasts in the marrow or blood, bleeding, susceptibility to infections, anemia).

Bone marrow

 * Hypercellular marrow with a pronounced predominance of granulopoetic elements, oppression of erythropoiesis,
 * the representation of megakaryocytes highly variable (CML can be divided into CGL - granulocytic and CGML - granulocytomegakaryocytic),
 * changes in stroma include the appearance of special collecting macrophage (called gaucheroid cells) or macrophages with hexagonal crystalloid formations in the cytoplasm (macroscopically the bone marrow is pyoid – i.e. similar to pus),
 * In forms with the multiplication of megakaryocytes, the multiplication of reticular fibers to myelofibrosis often leads to secondary thinning of bone beams.

Extramedullary tissue

 * Spleen – sinuses infiltrated by elements of granulopoiesis, or megakaryocytes, pronounced splenomegaly (up to 10 kg – the most pronounced enlargement of the spleen is precisely in CML),
 * liver – infiltration mainly in sinuses (unlike CLL, when infiltration is mainly in portobilia),
 * nodules – diffuse infiltration by leukemia cells (only in late stages).

Schéma translokace|thumb|200px

Finding in peripheral blood

 * High leukocytosis (50-250×109/l), Leukemic hiatus typical of AML
 * is missing (all the developmental stages of granulocytes are found in the differential).
 * A high number of leukocytes increases blood viscosity, which causes a decrease in blood flow to blood arrest (leukostasis)


 * It differs from the leukemia reaction (a condition resembling leukemia, when there are few mature white blood cells in the blood due to infection) with low leukocytic AF activity and the presence of a Ph-chromosome.
 * The number of platelets can be normal, increased and decreased.

Clinical manifestations
Clinically, three stages of the disease are distinguished: the chronic phase, the acceleration phase, the blast reversal phase. Symptoms of CML are nonspecific, include weight loss, temperature, sweating, loss of appetite. Up to 40% of cases are diagnosed randomly, based on blood counts. Splenomegaly is often present from physical examination (in more than 50% of cases). In case of successful therapy, the size of the spleen returns to normal. Severe anemia is rarely present, on the contrary, we often find thrombocytosis.

Therapy
In CML therapy, busulfan, hydroxyurea and interferon-α. Hydroxyurea is still sometimes used in the pre-treatment phase of therapy to quickly reduce the amount of circulating tumor elements. The revolution in CML therapy was the discovery of imatinib, the first tyrosine kinase inhibitor. It purposefully inhibits the still active BCR-ABL tyrosine kinase, thus stopping the growth of the tumor clone. Other pharmaceuticals have also been approved for therapy: nilotinib, dasatinib.

Související články

 * Leukemie z vláskových buněk
 * Filadelfský chromozom
 * Imatinib