Leukemia Information
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).
1. 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:
- ALL accounts for 80% of all childhood leukemias with approximately 4,000 new cases per year.
- AML is the most common type of acute leukemia diagnosed in adults, accounting for 12,000 new cases each year. Acute promyelocytic leukemia (APL) is a subtype of AML that accounts for 5–8% of AML in adults.
- CLL most often affects older adults with more than 15,000 new cases identified each year; it is rarely seen in children.
- CML accounts for approximately 5,000 new cases per year and occurs in all age groups. The median age of onset is 67 years.
- Other rare types of leukemia account for fewer than 6,000 new cases per year.
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
2. 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 cellsfrom 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,
3. 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:
- Conventional cytogenetics
- Fluorescent in situ hybridization (FISH)
- Polymerase Chain Reaction (PCR)
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.
4. 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
5. Guidlines
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:
http://www.nccn.org/professionals/physician_gls/f_guidelines.asp
The Guidelines for Europe can be found at European LeukemiaNet:
http://www.leukemia-net.org/content/home/
6. 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.
7. Additional Resources
For more information on leukemia, use the links below:
Lymphoma and Leukemia Society
http://www.lls.org/
Leukemia Research Foundation
http://www.leukemia-research.org/
American Society of Clinical Oncology
http://www.asco.org/
National Cancer Institute at the National Institute of Health
http://www.cancer.gov/cancertopics/types/leukemia
Centers for Disease Control and Prevention
http://www.cdc.gov/cancer/hematologic/leukemia/
European LeukemiaNet
http://www.leukemia-net.org/content/home/
World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia
http://bloodjournal.hematologylibrary.org/content/114/5/937.full