What is Leukemia?
Leukemia is a disease that affects the white blood cell progenitor cells, disturbing the mechanisms that regulate their synthesis and differentiation.
To understand this brief introduction it is necessary to know the basic concepts of hematopoiesis (a process that leads to the formation and maturation of blood cells starting from their precursors); let's see them in detail before going on to analyze the causes and symptoms of leukemia.
Hematopoietic marrow, stem cells and hematopoiesis
The hematopoietic cord
The cells circulating in the blood originate from stem precursors present in the bone marrow, a soft and "spongy" tissue that is found inside the hollow of the bones (present in the vertebrae, in the coasts, in the pelvis, in the skull and in the epiphyses of the long bones) .
Bone marrow is the main hematopoietic organ, therefore responsible for the formation of red blood cells (erythropoiesis), granulocytes (granulopoiesis, polymorphonuclear leukocytes - neutrophils, eosinophils and basophils), of monocytes (monocytopoiesis, from which tissue macrophages also derive), of lymphocytes (lymphocytopoiesis) and platelets (megakaryocytopoiesis).
The bone marrow, as actively proliferating, is very susceptible to radiation damage caused by radiation, cytostatic therapies or toxic environmental factors.
Stem cells
The hematopoietic stem cells present in the bone marrow have two fundamental properties:
- self-maintenance;
- Ability to differentiate.
The bone marrow, thanks to these characteristics, maintains throughout the life of the individual the ability to regularly replace the enormous number of senescent blood cells (after their introduction into the peripheral blood they undergo a progressive loss of replicative capacity) . This activity is performed by pluripotent hemopoietic stem cells, morphologically undifferentiated and capable of generating all the mature cells circulating in the peripheral blood. Pluripotent stem cells give rise to daughter cells that follow different paths: one will remain in a quiescent state and prevent exhaustion of the proportion of undifferentiated progenitors (equal to about 0.05% of the cells present in the bone marrow); the second will undergo a process of differentiation, giving rise to "committed" progenitors oriented in a myeloid or lymphoid sense , founders of the various blood supply chains.
Production of blood cells
During the first phase of the differentiation of hematopoietic stem cells, two cell lines are created that originate from the myeloid stem cell and the lymphoid stem cell . The first line leads to the formation of all blood cells (red blood cells, platelets, neutrophils, basophils, eosinophils and monocytes), with the exception of lymphocytes that derive from the second one.
The first stages of hematopoiesis are affected by the control by a series of growth factors, the so-called cytokines, synthesized and secreted by various medullary, stromal and immune system cells; these cytokines regulate the differentiation and proliferation of progenitor cells in a complex system of cooperation. The factor that stimulates the production of erythrocytes is erythropoietin (EPO), while to induce the production of leukocytes are colony-stimulating factors (CFU) and interleukins (IL).
Mature hematopoietic cells are released from the bone marrow into peripheral blood.
At the medullary level, the three main hematopoietic chains, namely the erythroid, the granulo-monocyte and the megakaryocyte one, produce, per day, about 3x109 erythrocytes / kg, 0.8x109 leukocytes / kg and 1.5 x109 platelets / kg respectively of body weight.
To sum up, the organization of the hematopoietic system is based on the presence of pluripotent stem cells (capable of generating all the mature cells of the peripheral blood) and, in succession, of stem cells with progressive restriction of the chain, up to the found cells of the single cellular series, which produce:
- white blood cells (or leukocytes): they are active elements of the immune system; perform a function of defense against pathogens of various kinds, to preserve the organism's biological integrity. There are different types of white blood cells (neutrophils, lymphocytes, monocytes, eosinophils and basophils; the term granulocytes groups neutrophils, eosinophils and basophils).
- red blood cells (or erythrocytes): they contain hemoglobin which carries oxygen and carbon dioxide in the body.
- platelets : important for hemostasis and the process of coagulation.
These cellular elements proliferate, grow old, undergo apoptosis and are replaced by new blood cells: leukocytes live only 1 day, platelets 4-6 days and erythrocytes about 120 days. Under normal conditions, there is a balance, modulated by hematopoietic growth factors, between the number of blood cells that undergo differentiation and the number that is destined to die.
Blood Cells
| Component | Primary function |
| Erythrocytes | Transport of O 2 and CO 2 |
| Leukocyte | Defense function against pathogens |
| Platelets | Haemostasis |
Circulating adult leukocytes include very different cell populations:
| Component | Quantity % | Primary function | Function in immunity |
| Neutrophils | 50-80% | Phagocytosis | Phagocyte microorganisms, abnormal cells and foreign particles. |
| Eosinophils | 1-4% | Destruction of pests | Contribute to defenses against parasitic infestations; participate in tissue damage in allergic reactions. |
| basophils | 1% | Production of chemical mediators during inflammation and allergic reactions | They release toxic molecules against invading agents and participate significantly in allergic reactions, releasing histamine, heparin to other compounds. |
| Monocytes | 2-8% | phagocytosis; mature in macrophages in tissues. | Secrete cytokines; phagocyte microorganisms. |
| Lymphocytes | 20-40% | B cells - secrete antibodies (Ab) and mediate the humoral immune response (depositors of immunological memory); T cells - induce a cell-mediated response, produce cytokines that support the immune response of other cells and factors that destroy infected or neoplastic cells. | Plasma cells (mature forms of B cells) produce Ab; T-helper lymphocytes produce cytokines that activate different cell types, amplifying the immune response; cytotoxic T cells attack infected or tumor cells and induce their lysis; natural killer (NK) cells produce factors that induce cell death of cells known to be infected and are able to kill some cancer cells. |
What is leukemia?
Leukemia is a neoplasm (tumor) of blood cells that affects the hematopoietic tissues of the body, including the bone marrow and the lymphatic system. The word " leukemia " comes from the Greek: leukos, "white" and aima, "blood", literally "white blood", since most of the leukemias involve a significant alteration of the morphology and function of leukocytes (white blood cells). Based on the clinical characteristics and the type of cells involved in the tumor process, leukemias are classified as acute, chronic, myeloid and lymphoid .
If the disease occurs, it is important to identify exactly which cells it comes from, as the prognosis and treatment options vary depending on the different type of cancer.
Leukemic cells
When an immature hematopoietic cell begins to reproduce in an uncontrolled manner, the onset of leukemia is favored: the bone marrow produces abnormal white blood cells (leukemia or tumor cells), consequently this cellular component does not perform the normal defensive function from infections and toxins reached from the outside. Furthermore, the development of red blood cells and platelets is "suffocated" by tumor clones. The differentiation of abnormal stem cells is faster and uncoordinated than normal cells, persisting even after the cessation of the stimuli that caused the mutation.
Over time, leukemia cells, which do not respond to normal control mechanisms, can expand in the bone marrow, flow into the bloodstream and significantly interfere with the growth and development of normal blood cells. This can lead to serious problems such as anemia, bleeding and infections. The uncontrolled proliferation of the leukemic cells also allows the spread to the lymph nodes or to other organs generating swelling or pain.
Types of Leukemia
Leukemias are classified according to the type of cells involved in the tumor process, the degree of maturation reached by the leukemia cells, the course of the disease and the characteristics of the clinical symptoms. From the point of view of clinical progress, they are classified as acute (with a very rapid course and more severe prognosis) or chronic (with a slow and progressive course, controllable with drug therapy). Another important distinction concerns the cells from which the tumor originates.
Based on the cell type affected by the proliferation, they are distinguished:
- lymphoid (or lymphatic) leukemia : when the tumor affects the lymphocytes or cells of the lymphoid line;
- myeloid leukemias : when the malignant transformation concerns the components of the myeloid lineage (erythrocytes, platelets and leukocytes).
The four main types of leukemia are:
- Acute lymphoblastic leukemia;
- Acute myeloid leukemia;
- Chronic lymphatic leukemia;
- Chronic myeloid leukemia.
Acute Leukemias
Acute leukemias are rapidly progressive diseases characterized by a rapid course and the early appearance of symptoms. In these neoplastic forms, there is an accumulation of immature cells at the level of the bone marrow and peripheral blood; the bone marrow, in fact, is no longer able to produce normal blood cells (leukocytes, erythrocytes and platelets). Acute leukemias usually present with hemorrhage, anemia, infection or organ infiltration.
- Acute myeloid leukemia (or AML) : the leukemic cells deriving from myeloid cell lines expand in the bone marrow and determine an alteration of the differentiation and proliferation of normal hematopoietic cells. The result is impaired production of erythrocytes (anemia), granulocytes (neutropenia) and platelets (thrombocytopenia). Later, blasts invade peripheral blood, infiltrating different organs.
- Acute lymphoblastic leukemia (or ALL) : it represents a clonal neoplastic disorder with very high aggressiveness, originating from lymphopoietic precursors in the bone marrow, in the thymus and in the lymph nodes. Lymphoblasts are not true blasts, but cells that are not yet completely differentiated. About 80% of the ALL are malignant proliferations of the B chain, while 20% include cadres resulting from the involvement of precursors of the T chain.
Chronic Leukemias
Chronic leukemias have a slower and more stable course over time than acute forms. They are characterized by the progressive accumulation, in the bone marrow and in the peripheral blood, of relatively mature cells, in part still functioning. In chronic forms proliferation is less rapid, only to become more aggressive with time, leading to the progressive increase of neoplastic clones within the bloodstream; all this correlates to the gradual worsening of the typical symptoms of leukemia. Many patients with chronic leukemias are asymptomatic, while in other cases the disease presents with splenomegaly, fever, weight loss, malaise, frequent infections, bleeding, thrombosis or lymphadenopathy. Some chronic leukemias tend to progress in a particular phase, where the clinical manifestations are similar to acute leukemias (example: blastic phase of chronic myeloid leukemia).
- Chronic myeloid leukemia (or CML) : derives from the neoplastic transformation of the pluripotent stem cell, which however retains the capacity to differentiate towards the leukocyte line. CML is characterized by the proliferation and progressive accumulation of mature granulocyte cells at the medullary level. Generally, the disease develops and progresses slowly, over months or years, even without treatment. CML is the rarest of the four main types of leukemia and is especially needed in adults.
- Chronic lymphocytic leukemia (or CLL ): it is a monoclonal proliferation of small lymphocytes (B), apparently mature, but immunologically non-functioning, circulating in the peripheral blood, in the bone marrow, in the spleen, in the liver and occasionally in other lymphatic or extra locations lymph. CLL is the most common form of occurrence in western industrialized countries and represents 25-35% of all human leukemia; it affects a male / female ratio of 2: 1 and elderly subjects over the age of 50.
Evolution
The severity of leukemia depends on the use of the disease, the response to medical therapy and the involvement of various organs. In general, five-year survival in lymphatic leukemia exceeds 63%, while in myeloid leukemia it is 26%.
