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Image: “Blood smear in CLL” by VashiDonsk at the English language Wikipedia. Licence: CC BY-SA 3.0


Types of Leukemia

Classification

Acute leukemias which can be of myeloid or lymphoid lineage

  • Acute lymphoblastic leukemia (ALL)
  • Acute myeloid leukemia (AML)

Chronic leukemias which can be of myeloid or lymphoid lineage

  • Chronic myelogenous leukemia
  • Chronic lymphocytic leukemia

Acute Lymphocytic Leukemia

This is the most common form of leukemia in children between 2 and 4 years of age. It rarely affects adults, though another incidence can occur in individuals over 45 years. The immature lymphocytes, mostly B-cells produced by the bone marrow, are incapable of providing immunity for the body. Thus, these lymphocytes travel to different organs and tissues and develop the symptoms of the disease.

Acute lymphoblastic leukemia of B-cell origin is the most common hematopoietic malignancy in children. About 80% of those cases show B-cell lineage, as confirmed by the expressions of CD19, CD79, and cyCD22 as well as lack of definitive myeloid differentiation. The leukemic form pertains to more than 20% of the lymphoblasts in the bone marrow; there may be more than 20% in the peripheral blood.

Almost all cases show extensive neoplastic lymphoblasts that have replaced the bone marrow, with a reduction of normal hematopoietic elements. In the case of a hypercellular marrow, more than 80% of the cells are represented by lymphoblasts. Patients present with any of the signs and symptoms of marrow failure, such as pallor and fatigue, caused by anemia, along with fever related to granulocytopenia, as well as petechiae and ecchymoses caused by thrombocytopenia.

Pre-B ALL Pre-T ALL
Frequency 80% 20%
Age of onset Childhood Adolescence
Site Blood/BM Mediastinal mass
WBC count Low-Normal High
Prognosis Good Poor
Symptoms Pancytopenia, neurologic symptoms, bone pain

Acute Myeloid Leukemia (nonlymphocytic leukemia)

This is a very aggressive, fast-growing blood and bone marrow cancer. The bone marrow suddenly begins producing immature blood cells of all types—red, white, platelets—which, with time, crowd the normal ones, so that a normal immune response to the infections becomes impossible. Since the changes occur over time, AML is usually diagnosed in young adults.

There is no clear cause of AML; however, there are several risk factors, including:

  • Genetic influence
  • Radiation exposure
  • Chemical exposure such as benzene
  • Drugs that induce secondary malignancies, such as dexrazoxane, have been implicated in AML development
  • Smoking and other occupational exposures, such as to petroleum products, paint, embalming fluids, ethylene oxide, herbicides, and pesticides, have also been associated with an increased risk of AML

There are subtypes of this kind of leukemia, according to the prevalence of the affected blood cells:

  • Myeloblastic (M0) – on a special analysis
  • Myeloblastic (M1) – without maturation
  • Myeloblastic (M2) – with maturation
  • Promyelocytic (M3)
  • Myelomonocytic (M4)
  • Monocytic (M5)
  • Erythroleukemia (M6)
  • Megakaryocytic (M7)

Chronic Lymphocytic Leukemia

CLL is a slowly growing blood and bone marrow cancer, which disturbs the production and maturation of lymphocytes and spreads to the lymph nodes, liver, and spleen. Some patients may be asymptomatic; however, most patients present with:

  • Splenomegaly
  • Lymphocytosis > 5000/uL
  • Matured lymphocytes
  • Co-expression of CD19 and CD5

Sometimes, it takes years for the disease to manifest because all the pathogenic processes are indolent. However, it can turn into an acute form, and then the prognosis worsens accordingly.

Image: "Diagram showing the cells CLL afects" by Cancer Research UK. License: CC BY-SA 4.0

Image: “Diagram showing the cells CLL afects” by Cancer Research UK. License: CC BY-SA 4.0

B-cell chronic lymphocytic leukemia is the most common chronic leukemia in adults in Western countries. Most cases involve blood and bone marrow, with or without the involvement of lymph nodes, spleen, liver, and other organs. The neoplastic lymphocytes are small but slightly larger than normal small lymphocytes.

They show scant cytoplasm and round, to slightly irregular, nuclei, containing clumped chromatin. Nucleoli are small to indistinct. A characteristic morphologic feature is “smudge” or “basket” cells, which are essentially neoplastic cells that got “smudged” during slide preparation because of their fragility. Compare the size of CLL cells with a single large granular lymphocyte.

Chronic Myeloid Leukemia

CML, unlike the other types of leukemia, has a distinguishing feature which makes this condition stand out from among this group.

The age-adjusted incidence is higher in men than in women (1.7 versus 1.0). The incidence of CML increases slowly with age until the middle forties when it starts to rise rapidly. Chronic myelogenous leukemia (CML) accounts for 20% of all adult leukemias.

CML is associated with an abnormal chromosome, known as the Philadelphia chromosome (Ph chromosome-abnormal cancer chromosome). It occurs when a piece of chromosome 22 breaks off and joins to the end of chromosome 9, which also breaks off and reattaches to chromosome 22. This type of leukemia, just like the other ones, affects the blood and the bone marrow.

Chronic myelogenous leukemia is a clonal chronic myeloproliferative disorder. It results in an absolute increase in granulocytic cells, including neutrophils, eosinophils, and basophils. It is caused by fusing a portion of the BCR gene on chromosome 22q with a portion of the ABL1 gene that is translocated from chromosome 9q34, thus forming what is known as the Philadelphia chromosome. The resulting fused tyrosine kinase protein, BCR-ABL, has constitutive proliferative activity. The marrow is markedly hypercellular, with an elevated myeloid to erythroid ration often exceeding 10:1.

Differentiating Leukemias

ALL AML CML CLL
Age Children Young adults Middle-age Elderly
Onset Abrupt/Acute Chronic/Insidious
Symptoms Cytopenias, bone pain Non-specific, fatigue, weakness, etc.
Prognosis Excellent (2/3 cured) Moderate (30% cured) OK with imatinib; otherwise poor Poor, but slowly progressing

Hairy Cell Leukemia

This rare subtype of chronic lymphocytic leukemia (CLL) is an indolent form of blood cancer. The whole essence of the condition is that the bone marrow produces far too many B-lymphocytes, which crowd the other types of blood cells. These immature B-cells are unable to protect the body from infectious invaders.

The disease name comes from the cells’ specific appearance under a microscope. This illness is very peculiar because, at the initial stages, there are no severe symptoms, so it might not require treatment. However, as the disease progresses, treatment is essential.

Hairy cell leukemia smear

Image: “Hairy cell leukemia: abnormal B cells look “hairy” under a microscope because of radial projections from their surface.” by Paulo Henrique Orlandi Mourao. License: CC BY-SA 3.0

Hairy cell leukemia (HCL) is a rare, mature B-cell neoplasm, which involves the bone marrow and spleen. Generally, only a few circulating cells are seen on peripheral blood smears. Bone marrow involvement can be interstitial, patchy, or diffuse (as in this case) depending on the extent of involvement. Because of marrow involvement, most patients present with pancytopenia and splenomegaly. Monocytopenia is also common. Absolute lymphocytosis may occur in up to 25% of the patients. Lymphadenopathy and hepatomegaly may also occur.

Myelodysplastic Syndromes

The bone marrow produces far too few blood cells of all types. They look dysplastic under a microscope (getting the name for the condition); thus, they are unable to function in the body. Sometimes, this disease is called preleukemia; however, true leukemia never develops from this condition. Myelodysplastic syndromes are associated with severe bleeding and infections.

hypogranular_neutrophil_with_a_pseudo-pelger-huet_nucleus_in_mds

Bone marrow: Therapy-related myelodysplastic Syndrome: Blood smear from an adult female with a myelodysplastic syndrome related to radiotherapy and chemotherapy for Hodgkin disease. A hypogranular neutrophil with a pseudo-Pelger-Huet nucleus is shown. The red blood cells show marked poikilocytosis, in part related to post-splenectomy status. (Wright-Giemsa stain)

Etiology and Risk Factors

The causes of myelodysplastic syndromes is unknown. However, risk factors include:

  • Predisposing hematological disorder (myelodysplastic syndrome)
  • Family history of malignant blood disease
  • Receiving chemotherapy or radiotherapy treatment
  • Exposure to aggressive cancerogenic chemicals (benzene or radiation)
  • Smoking
  • Down syndrome and Fanconi anemia
  • Having a sibling with leukemia

Epidemiology

Leukemia incidence is highest among Caucasians and lowest among East Asians (Chinese, Japanese, and Koreans). There is a 50% higher incidence of leukemia in men than women. Also, older age contributes to the danger of contracting this disease. Leukemia is diagnosed in about 29,000 adults and 2,000 children in the United States annually. The individuals most susceptible to childhood leukemia are of Filipino descent, followed by white Hispanics, non-Hispanic whites, and African Americans, accordingly.

Most Common Symptoms and Signs

  • Fatigue
  • Night sweats
  • Sudden high-grade fever
  • Sound pallor
  • Bruising or bleeding after an insignificant injury and petechiae (flat, pinpoint spots under the skin)
  • Significant weight loss
  • Loss of appetite
  • Breathlessness (lymphoblastic forms)
  • Bone or stomach pain (ALL)
  • Pain or a feeling of fullness below the ribs (ALL, CML)
  • Diffuse lymphadenopathy, non-painful lumps in the neck, under the arms, stomach or groin (lymphoblastic forms), though there may be painful, swollen lymph nodes (CLL)
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