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The effect of cytokines, including IL4, IL7, stem cell factor, insulin-like growth factor on childhood acute
R Consolini1, A Legitimo, M Cattani
1Department of Pediatrics, University of Pisa, Italy.
Insights
Interleukin 7 (IL7) and other growth factors show varied effects on acute lymphoblastic leukemia (ALL) cell growth and differentiation. Some ALL cells responded to IL7, with limited maturation observed in others, while IL4, SCF, and IGF-1 had minimal impact.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Human lymphopoiesis involves key cytokines like IL7, SCF, and IGF-1.
- Acute lymphoblastic leukemia (ALL) is a cancer of immature lymphocytes.
- Pre-B cell lines and primary ALL blasts are used to study leukemia development.
Purpose of the Study:
- To investigate the effects of IL4, IL7, SCF, and IGF-1 on ALL cell proliferation, clonal growth, and differentiation.
- To determine the potential of these cytokines to induce maturation in ALL cells.
- To explore the role of these factors in B-cell precursor ALL (BCP ALL).
Main Methods:
- Culturing Nalm 1 and Nalm 6 pre-B cell lines.
- Analyzing purified blasts from 37 childhood ALL patients.
- Assessing cell proliferation, clonal growth, and differentiation markers (surface immunoglobulins, terminal deoxynucleotidyl transferase, cALL antigen) after cytokine treatment.
Main Results:
- IL4 showed no promoting activity and inhibited growth in some patients.
- IL7 induced proliferation and clonal growth in a minority of ALL cases, with heterogeneous responses.
- IL7 demonstrated potential for limited ALL cell maturation, indicated by changes in differentiation markers, but did not consistently induce surface immunoglobulin expression.
- SCF did not enhance IL7 response in BCP ALL.
- IGF-1 alone or with IL7 did not induce proliferation or clonal growth in BCP ALL.
Conclusions:
- Cytokine responsiveness in ALL cells is highly variable.
- IL7 may possess limited differentiation-inducing capacity in a subset of ALL patients.
- SCF and IGF-1 do not appear to be effective in promoting proliferation or growth in BCP ALL under these conditions.
Abstract:
We have investigated the effects of some interleukins, such as interleukin (IL) 4, IL7, stem cell factor (SCF) and insulin-like growth factor (IGF-1), known to be involved in human lymphopoiesis, on proliferation, clonal growth and differentiation of cells from two acute lymphoblastic leukemia (ALL) derived pre-B cell lines, that is, Nalm 1, Nalm 6 and purified blasts from 37 childhood ALL. IL4 did not display any promoting activity, an inhibitory effect being observed in two patients. IL7 showed an heterogeneous responsiveness, not related to immunophenotype or cytogenetic features, proliferation and clonal growth being observed in a minority of ALL. In other patients no or even inhibitory effects on proliferation were observed. In one case this inhibition of DNA synthesis was accompanied by maturation of the cells, as demonstrated by the induced expression of surface immunoglobulins (slg); other IL7 treated samples failed to express slg, but showed a decreased expression of terminal deoxynucleotidyl transferase and cALL antigen, suggesting that the cells have a potential of limited maturation by IL7. SCF, known to synergize with IL7 in the most primitive stages of normal B cell development, did not enhance the IL7 response in B cell precursor ALL. Finally IGF-1 failed to induce a proliferative response and clonal growth in BCP ALL either alone or in combination with IL7.
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