2023 Jan 17. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–.
ABSTRACT
The production of abnormal leukocytes defines leukemia as either a primary or secondary process. They can be classified as acute or chronic based on the rapidity of proliferation and myeloid or lymphoid based on the cell of origin. Predominant subtypes are acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), involving the myeloid lineage; acute lymphoblastic leukemia (ALL); and chronic lymphocytic leukemia (CLL), involving the lymphoid chain. Other less common variants, such as mature B-cell and T-cell leukemias, and NK cell-related leukemias, to name a few, arise from mature white blood cells. However, with the advent of next-generation sequencing (NGS) and the identification of various biomarkers, the World Health Organization (WHO) classification was updated in 2016, bringing multiple changes to the traditional classification for acute leukemias and myeloid neoplasms. GLOBOCAN, a global observatory for cancer trends, showed a global incidence of 474,519 cases, with 67,784 in North America. The Age-Standardized Rates are around 11 per 100,000, with a mortality rate of approximately 3.2.
Many genetic risk factors have been identified, such as Klinefelter and Down syndromes, ataxia telangiectasia, Bloom syndrome, and telomeropathies such as Fanconi anemia, dyskeratosis congenita, and Shwachman-Diamond syndrome; germline mutations in RUNX1, CEBPA, to name a few. Viral infections associated with Epstein Barr virus, human T-lymphotropic virus, ionizing radiation exposure, radiation therapy, environmental exposure with benzene, smoking history, history of chemotherapy with alkylating agents, and topoisomerase II agents have also been implicated in the development of acute leukemias. Symptoms are nonspecific and can include fever, fatigue, weight loss, bone pain, bruising, or bleeding. Definitive diagnoses often require bone marrow biopsy, the results of which help the hematologists and stem cell transplant physicians regarding the selection of treatment options ranging from chemotherapy to allogeneic stem cell transplantation. The prognosis is variable depending on the leukemia subtype in question.
Acute vs. chronic myeloid leukemia: Blasts, which are immature and dysfunctional cells, normally make up 1% to 5% of marrow cells. Acute leukemias are characterized by greater than 20% blasts in the peripheral blood smear or on bone marrow leading to a more rapid onset of symptoms. In contrast, chronic leukemia has less than 20% blasts with a relatively chronic onset of symptoms. The accelerated/blast phase is a transformation of chronic myeloid leukemia into an acute phase with a significantly higher degree of blasts.
As such, the four major subtypes of leukemia are:
Acute lymphoblastic leukemia (ALL): ALL is seen in patients with the blastic transformation of B and T cells. It is the most common leukemia in the pediatric population, accounting for up to 80% of cases in this group vs. 20% of cases in adults. Treatment among adolescents and young adults is predominantly inspired by pediatric regimens with better survival rates.
Acute myelogenous leukemia (AML): AML is characterized by greater than 20% myeloid blasts and is the most common acute leukemia in adults. It is the most aggressive cancer with a variable prognosis depending upon the molecular subtypes.
Chronic lymphocytic leukemia (CLL): CLL occurs from the proliferation of monoclonal lymphoid cells. Most cases occur in people between the ages of 60 and 70. CLL is considered an indolent disease, for the most part, meaning not all patients with a diagnosis will need to start treatment until symptomatic from the disease.
Chronic myelogenous leukemia (CML): CML typically arises from reciprocal translocation and fusion of BCR on chromosome 22 and ABL1 on chromosome 9, resulting in dysregulated tyrosine kinase on chromosome 22 called the Philadelphia (Ph) chromosome. This, in turn, causes a monoclonal population of dysfunctional granulocytes, predominantly neutrophils, basophils, and eosinophils.