Leukemia

Explore the complex world of leukemia.

As a service to our customers, we offer an overview of this complicated cancer, from epidemiology and diagnosis to guidelines and additional resources. We hope you find it helpful.

Leukemia is a heterogeneous group of cancers of the white blood cells.

Lymphocytic leukemia derives from lymphoid cells, and myelogenous leukemia from myeloid cells….. Leukemia can be acute or chronic; in general acute leukemia progresses rapidly while chronic leukemia progresses more slowly. The four most common types of leukemia are chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphocytic leukemia (ALL), and acute myeloid leukemia (AML). 

Contents


Epidemiology

Worldwide, an estimated 350,000 people are diagnosed with leukemia each year, with approximately 257,000 deaths annually. In the United States, there were approximately 43,050 new cases of leukemia, and 21,840 deaths in 2010 [1]. Leukemia is the primary cause of deaths from cancer in children and young adults under the age of 20 years. The incidence of various leukemias in the US is as follows:

Find more leukemia facts and figures at Surveillance Epidemiology and End Results:

http://seer.cancer.gov/

http://globocan.iarc.fr/factsheets/populations/factsheet.asp?uno=900


Genetics

Leukemias and other related blood-based neoplasms are complex and heterogeneous diseases involving a variety of blood cell types such as monocytes, granulocytes, erythrocytes, megakaryocytes, B-cells, T-cells, or NK-cells. Traditionally, morphologic, cytochemical, and immunophenotypic features are used to determine the lineage of the neoplastic cells and their maturation stage. In addition, distinct genetic alterations and structural rearrangements of the chromosomes have been used to distinguish and classify the various types and sub-types of leukemias. With the recent advances in molecular techniques and a better understanding of the human genome, more genetic alterations have been precisely characterized. These alterations can be very large resulting in chromosomal rearrangements such as translocations, deletions, duplications, or inversions. In other cases, the genetic alterations can be minute involving only a few bases of the genomic DNA such as small insertions, repeated sequences, or individual point mutations.

Specific genetic alterations are directly involved in the pathogenesis of leukemia, i.e. they directly affect the normal maturation of hematopoietic stem cells, the multipotent stem cells from which all the blood cell types are derived. As a consequence, genetic information is critical for the accurate diagnosis and classification of leukemias and the selection of personalized treatment options. Literally hundreds of genetic alterations are documented in the scientific literature and many are currently used in the management of leukemias [2]. As additional markers and new clinical study results are reported on a weekly basis, clinical practice guidelines must be continuously updated. The classification of myeloid neoplasms and acute leukemia based on morphologic, cytochemical, immunophenotypic, and genetic information published by the World Health Organization (WHO) in 2008 can be found at http://bloodjournal.hematologylibrary.org/content/114/5/937.full.


Diagnosis

The diagnosis of leukemia at presentation is based on symptomatic examination and evaluation of the size, number and maturity of various cell types in peripheral blood and bone marrow specimens. In addition, cytogenetic abnormalities, especially chromosomal translocations, are frequently observed in leukemia. Gene mutations are also important factors in leukemia pathogenesis. Assessment of genetic abnormalities provides information regarding disease subtypes, potential therapeutic options, and prognosis. As a consequence, detecting genetic abnormalities in conjunction with other laboratory characterization is an established practice in diagnosing leukemia.

Diagnosis. Molecular characterization of the cancer can be assessed by testing blood or bone marrow specimens using methods such as:

Monitoring. During treatment, the efficacy of a specific therapy regimen can be monitored by testing for the presence of genetic abnormalities identified at the initial diagnosis. Monitoring can be performed by cytogenetic methods on blood or bone marrow specimens but requires more sensitive and quantitative PCR-based molecular methods to detect low levels of residual disease.

Risk Assessment. Several parameters such as age, general health status, blood cell count at diagnosis or initial response to treatment have a prognostic value, i.e. can aid in the prediction of whether the clinical outcome will be favorable or unfavorable. In addition, specific genetic abnormalities are associated with good or poor prognosis. Accurate detection of these abnormalities at diagnosis constitutes the foundation of the modern classification and management of leukemias based on risk assessment.


Therapy

There are multiple treatment options for leukemia depending upon the type of leukemia and the patient’s age. Acute leukemia progresses rapidly and requires a more aggressive approach to treatment than chronic leukemia, which progresses more slowly. Therapeutic options include watchful waiting, chemotherapy, targeted therapy, biological therapy, radiation therapy, and stem cell transplantation. Improved understanding of the molecular processes that control cancer cells is enabling the development of new targeted therapies. Such targeted therapies exploit the products or pathways that are associated with the observed mutations and cytogenetic alterations. To be most effective, these new targeted therapies require accompanying molecular tests to detect genetic abnormalities at initial diagnosis, select the most appropriate therapy, and monitor response to the personalized treatment for a specific type or sub-type of leukemia.

For more information on leukemia therapies, go to http://www.cancer.gov/cancertopics/types/leukemia


Guidelines

The National Comprehensive Cancer Network (NCCN) guidelines support the use of genetic tests along with traditional morphology and immunophenotype assessment. NCCN clinical guidelines can be accessed through the link below. They are free to download but you must first login or register.

National Comprehensive Cancer Network

The Guidelines for Europe can be found at European LeukemiaNet


References

Jemal, A., R. Siegel, J. Xu, and E. Ward, Cancer statistics, 2010. CA Cancer J Clin, 60(5): p. 277-300.2010.

Swerdlow, S.H., E. Campo, N.L. Harris, E.S. Jaffe, S. Pileri, and H. Stein, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 2008, International Agency for Research on Cancer.

Leitner, A.A., A. Hochhaus, and M.C. Muller, Current treatment concepts of CML. Curr Cancer Drug Targets, 11(1): p. 31-43.2011.

Leitner, A.A., A. Hochhaus, and M.C. Muller, Current treatment concepts of CML. Curr Cancer Drug Targets, 11(1): p. 31-43.2011.

Marcucci, G., T. Haferlach, and H. Dohner, Molecular genetics of adult acute myeloid leukemia: prognostic and therapeutic implications. J Clin Oncol, 29(5): p. 475-86.2011.

Falini, B., Acute myeloid leukemia with mutated nucleophosmin (NPM1): molecular, pathological, and clinical features. Cancer Treat Res, 145: p. 149-68.2010.

Jemal, A., R. Siegel, J. Xu, and E. Ward, Cancer statistics, 2010. CA Cancer J Clin, 60(5): p. 277-300.2010.


Additional resources

For more information on leukemia, use the links below:

 

 

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