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Note: This section has health/medical information. It was not written by a health care professional. The medical references are:
- Childhood Leukemias, edited by Ching-Hon Pui, 1999, Cambridge University Press
- NCI web site section on ALL, accessed 2010
After finding out that their child has ALL leukemia, parents then learn which type of ALL it is according to the immunophenotype (or simply "phenotype"). Most ALL leukemias fall into one of the following 4 types:
- early pre-B
The phenotype is important in that it determines the treatment that the child will receive. Over the several decades that they have been successfully treating ALL, researchers have found that each of the 4 main phenotypes of ALL responds differently to treatment. The prognosis for T- and B-cell ALL used to be worse than for the pre-B ALLs; today, the prognosis is becoming even across the phenotypes because the current protocols treat the different types with different protocols.
How they determine the phenotype
The phenotype is determined by a technique called flow cell cytometry. Briefly, this is a machine that determines which antigens (proteins) are expressed on the surface of the leukemia cell. These antigens have the names CD2, CD3, CD7, CD5, HLA-DR, etc. Please see the following link for technical details:
- flow cytometry in the MRD section on this ped-onc site
B-lineage ALL cells express the antigens called CD19, HLA-DR, and/or CD10 (cALLa). About 80% of the pre-B cell ALLs express the cALLa antigen, often called "common ALL antigen", which is generally associated with a favorable prognosis.
B-lineage ALL is further classified into three subtypes that reflect the stage of maturation of the leukemic B-cell. In B-lineage ALL, what has happened is that one solitary uncommitted stem cell floundered somewhere in the pathway to becoming a mature B type plasma cell. As a stem cell goes through the "pathway", it will express different antigens on its surface and may express immunoglobins (SIg for surface immunoglobin, CyIg for cytoplasmic immunoglobin) . So thus depending on where in the pathway the cell deviates into uncontrolled growth, the ALL clone will have a characteristic pattern of antigens/immunoglobins as determined by flow cytometry. The three major types of B-lineage cells found in childhood ALL are:
- early pre-B, no SIg or CyIg, usually has CD10
- pre-B, has CyIg, usually has CD10
- B-cell, has SIg, might have CD10
Complete panels of antigen expression are available on a few web sites:
- excellent link on this topic: Hematopathologic Phenotypes Made Mockingly Simple, A remedy for CDphobia, by Margaret Uthman, MD.
- another link that describes leukemia and lymphoma flow cytometry panels on the University of Washington hematopathology lab web site.
- from the Rubnitz/Pui article in The Oncologist
Early pre-B and pre-B ALL are the most common types of childhood ALL. B-cell ALL accounts for less than 5% of childhood ALL cases and is treated on protocols for non-Hodgkins lymphoma.
More on the maturation of B-cells and the expression of antigens in on the ped-onc page on clonality (in the MRD section).
T-cell ALL is defined by the leukemic cell expression of the T-cell associated antigens called CD2, CD7, CD5, or CD3. Of these, CD2 is associated with a more favorable prognosis. T-cell ALL and is often associated with certain diagnostic variables, such as male sex, older age, higher white blood cell count at diagnosis, and mediastinal mass. Approximately 15% of newly diagnosed children with ALL have the T-cell phenotype.
T cells develop in the thymus rather than in the bone marrow.
Leukemic cells can also be classified according to morphology, although "due to the lack of independent prognostic significance and the subjective nature of this classification system, it is no longer used in the United States" (cancer.gov web site, 7/2005). French-American-British (FAB) convention describes leukemic cells as L1, L2, or L3. The occurrence of these are: L1 80-85%, L2 15%, L3 1-3% L1 morphology tends to the best prognosis; L3 morphology is indistinguishable from B-cell Burkitt's lymphoma cells (NHL).
These pages are intended for informational purposes only and are not intended to render medical advice. The information provided on Ped Onc Resource Center should not be used for diagnosing or treating a health problem or a disease. It is not a substitute for professional care. If you suspect your child has a health problem, you should consult your health care provider.