Relations Between Il-3-Induced Proliferation and in Vitro Cytokine Secretion of Bone Marrow Cells From Aml Patients

Nowak, Ralf; Oelschlägel, Uta; Gurth, Heidrun; Range, Ursula; Albrecht, Steffen; Krebs, Uwe; Hietschold, Volker; Ehninger, Gerhard

doi:10.1006/cyto.1998.0445

Cited by 10 publications

(12 citation statements)

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“…74,75 In a study carried out on 53 AML patients, clearly detectable levels of IL-3 have been detected in about 80% of the leukemic blast cell culture supernatants. 76 The highest IL-3 secreting capacity was observed in M1/M2/M3 AMLs. 76 It is of interest to note that in this study was reported the capacity of IL-3 to stimulate the production of secondary cytokines, such as IL-6, TNF-a and IL-1b by leukemic cells.…”

Section: Il-3r In Acute Leukemiamentioning

confidence: 96%

“…76 The highest IL-3 secreting capacity was observed in M1/M2/M3 AMLs. 76 It is of interest to note that in this study was reported the capacity of IL-3 to stimulate the production of secondary cytokines, such as IL-6, TNF-a and IL-1b by leukemic cells. 76 Interestingly, IL-3 or GM-CSF IL-3R in acute leukemia U Testa et al production by leukemic blasts was observed also at the level of early progenitor leukemic cells, that is, at the level of the leukemic blasts that initiate and maintain the leukemic process.…”

Section: Il-3r In Acute Leukemiamentioning

confidence: 96%

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Interleukin-3 receptor in acute leukemia

et al. 2003

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Recent studies indicate that abnormalities of the interleukin-3 receptor (IL-3R) are frequently observed in acute myeloid leukemias (AMLs) and may contribute to the proliferative advantage of leukemic blasts. This review analyzes the evidences indicating that the IL-3R represents one of the target molecules involved in the stimulation of proliferation of AMLs, and the overexpression of the IL-3Ra chain may represent one of the mechanisms contributing to the development of a highly malignant leukemic phenotype. Furthermore, there is evidence that the IL-3Ra is a marker of leukemic stem cells, at variance with normal stem cells that are IL-3Ra À . Finally, the IL-3R may represent an important target for the development of new antileukemic drugs.

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Section: Il-3r In Acute Leukemiamentioning

confidence: 96%

Section: Il-3r In Acute Leukemiamentioning

confidence: 96%

Interleukin-3 receptor in acute leukemia

et al. 2003

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“…High expression of the IL-3 receptor has been noted in leukemic blasts [6] and correlates with enhanced cycling of blasts and poor patient oucomes [7]. IL-3 is frequently expressed by leukemic myeloblasts [8] and can promote clonogenicity of primary blasts [9]. IL-3 production by imatinib resistant CML blasts can render other leukemic blast cells resistant through paracrine stimulation [10].…”

Section: Introductionmentioning

confidence: 99%

IL-3 and Oncogenic Abl Regulate the Myeloblast Transcriptome by Altering mRNA Stability

et al. 2009

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The growth factor interleukin-3 (IL-3) promotes the survival and growth of multipotent hematopoietic progenitors and stimulates myelopoiesis. It has also been reported to oppose terminal granulopoiesis and to support leukemic cell growth through autocrine or paracrine mechanisms. The degree to which IL-3 acts at the posttranscriptional level is largely unknown. We have conducted global mRNA decay profiling and bioinformatic analyses in 32Dcl3 myeloblasts indicating that IL-3 caused immediate early stabilization of hundreds of transcripts in pathways relevant to myeloblast function. Stabilized transcripts were enriched for AU-Response elements (AREs), and an ARE-containing domain from the interleukin-6 (IL-6) 3′-UTR rendered a heterologous gene responsive to IL-3-mediated transcript stabilization. Many IL-3-stabilized transcripts had been associated with leukemic transformation. Deregulated Abl kinase shared with IL-3 the ability to delay turnover of transcripts involved in proliferation or differentiation blockade, relying, in part, on signaling through the Mek/Erk pathway. These findings support a model of IL-3 action through mRNA stability control and suggest that aberrant stabilization of an mRNA network linked to IL-3 contributes to leukemic cell growth.

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“…on May 12, 2018. by guest www.bloodjournal.org From have been found to secrete cytokines, including IL-3. [45][46][47] Mechanistically, high proliferation of IL-3R␣-overexpressing AML cells is positively correlated with the level of IL-3-stimulated and spontaneous STAT5 activation. 31,43,44 In this context, because IL-3 signaling is strongly JAK2/STAT5 dependent, we believe that FA-AML cells share this common pathway, as our data suggest (Figures 5-6).…”

Section: Il-3r␣ Expression In Fa-aml Leukemia-initiating Cells 4247mentioning

confidence: 99%

Overexpression of IL-3Rα on CD34+CD38− stem cells defines leukemia-initiating cells in Fanconi anemia AML

Xue

Sipple

et al. 2011

Blood

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Patients with Fanconi anemia (FA) have a high risk of developing acute myeloid leukemia (AML). In this study, we attempted to identify cell-surface markers for leukemia-initiating cells in FA-AML patients. We found that the IL-3 receptor-␣ (IL-3R␣) is a promising candidate as an leukemia-initiating cell-specific antigen for FA-AML. Whereas IL-3R␣ expression is undetectable on normal CD34 ؉ CD38 ؊ HSCs, it is overexpressed on CD34 ؉ CD38 ؊ cells from FA patients with AML. IntroductionAcute myeloid leukemia (AML), a heterogeneous group of hematologic malignancies characterized by an accumulation of clonal myeloid progenitor cells that do not differentiate normally, 1,2 comprises approximately 25% of childhood acute leukemias. 3 The treatment of AML remains a challenge, and most AML patients will die of their disease within 1-2 years of diagnosis. 4 Conventional chemotherapeutic agents have been successful to some degree in treating AML, but now appear to have reached their maximum potential. Even with high-dose chemotherapy, only 30%-40% of AML patients survive, which is due mainly to relapse of the disease. 5 Recently, novel therapeutic strategies for AML have focused on immune-based therapy through monoclonal antibodies that target and destroy leukemic blasts via specific cell receptors. 6,7 These therapies were designed with the aim of selectively killing malignant cells that express unique antigens while sparing normal cells.One of the recent advances in the AML field is the postulation that AML arises from a rare population of leukemic stem cells (LSCs). 8,9 Phenotypic and functional analyses show that LSCs reside in the CD34 ϩ CD38 Ϫ compartment, the primitive stem/ progenitor population that also contains normal HSCs. 10 Further studies demonstrated that both normal HSCs and LSCs share the properties of quiescence and self-renewal. [8][9][10] This relatively dormant property of LSCs may contribute to the pattern of remission and subsequent relapse that is typical of the response to cytotoxic chemotherapy in AML. Therefore, it is believed that although most AML blasts can be eradicated by cytotoxic therapy, LSCs may be resistant to killing by chemotherapeutic agents. Recent studies have suggested that several antigens, such as CD33, CD44, CD96, CD123, and CLL-1, are specifically expressed in AML LSCs but not in normal HSCs. [11][12][13][14][15][16][17] Because it is believed that LSCs are the most relevant target population for novel antileukemic therapy, these unique antigens present opportunities for selectively targeting AML LSCs.One of the best studied AML models is Fanconi anemia (FA), a genetic disorder associated with bone marrow failure, clonal proliferation of HSCs and progenitor cells, and progression to myelodysplastic syndrome (MDS) and AML. [18][19][20] FA is caused by a deficiency in any of the 14 genes that encode the FANCA, FANCB, FANCC, FANCD1/BRCA2, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ/BRIP1, FANCL, FANCM, FANCN/PALB2, and FANCO/RAD51C proteins. [21][22][23][24] The biologic function ...

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Relations Between Il-3-Induced Proliferation and in Vitro Cytokine Secretion of Bone Marrow Cells From Aml Patients

Cited by 10 publications

References 0 publications

Interleukin-3 receptor in acute leukemia

Interleukin-3 receptor in acute leukemia

IL-3 and Oncogenic Abl Regulate the Myeloblast Transcriptome by Altering mRNA Stability

Overexpression of IL-3Rα on CD34+CD38− stem cells defines leukemia-initiating cells in Fanconi anemia AML

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