The effects of recombinant CSF‐1 on the blast cells of acute myeloblastic leukemia in suspension culture

Miyauchi, Jun; Wang, Chen; Kelleher, CC; Wong, Gordon G.; Clark, Steven C.; Minden, Mark D.; McCulloch, E. A.

doi:10.1002/jcp.1041350108

Cited by 76 publications

(41 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[15][16][17][18][19][20][21] From these in vitro studies it has been suggested that these growth factors also may play an essential role in the in vivo proliferation of most AML cells.…”

Section: Figurementioning

confidence: 99%

Proliferative effects of several hematopoietic growth factors on acute myelogenous leukemia cells and correlation with treatment outcome

Tsuzuki

Maruyama

et al. 1997

Leukemia

View full text Add to dashboard Cite

The response of human acute myelogenous leukemia (AML) cells to four different hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 ␤ (IL-1␤), interleukin-3 (IL-3), and stem cell factor (SCF)) and the relationship of the proliferative response of the AML cells to treatment outcome were studied. Proliferative responses were analyzed in 79 patients with de novo AML and 19 patients with AML arising from myelodysplastic syndrome (MDS). In de novo AML, a positive proliferative response (stimulation index Ͼ2) was seen in 65 to 75% of cases. AML cells arising from MDS had a much higher incidence of proliferative response to each growth factor (79 to 90%) and a much higher level of 3 H-TdR incorporation. The relationship to treatment outcome was evaluated in 79 patients with de novo AML. The patients whose leukemic cells had a positive proliferative response to any growth factor, especially IL-3 and SCF, had a poorer outcome, ie a lower complete remission (CR) rate, shorter CR duration, and shorter survival. The outcome was particularly poor in patients whose leukemic cells had proliferative responses to all four or any of the growth factors, compared to patients whose leukemic cells had no response. This increased response may be a marker of poor prognosis in patients with AML.

show abstract

“…[15][16][17][18][19][20][21] From these in vitro studies it has been suggested that these growth factors also may play an essential role in the in vivo proliferation of most AML cells.…”

Section: Figurementioning

confidence: 99%

Proliferative effects of several hematopoietic growth factors on acute myelogenous leukemia cells and correlation with treatment outcome

Tsuzuki

Maruyama

et al. 1997

Leukemia

View full text Add to dashboard Cite

show abstract

“…6 More particularly, recombinant IL-3 and granulocyte macrophage-CSF (GM-CSF) induce leukemic colonies and activate DNA synthesis in more than 80% of AMLs. [7][8][9][10] No clear relationship between IL-3 and GM-CSF responses and the French-American-British (FAB) classification of acute leukemias was observed. 6 Furthermore, leukemic cells may produce one or more of the principal HGFs, including IL-3 and GM-CSF.…”

Section: Introductionmentioning

confidence: 99%

Elevated expression of IL-3Rα in acute myelogenous leukemia is associated with enhanced blast proliferation, increased cellularity, and poor prognosis

Testa

Riccioni

Militi

et al. 2002

Blood

290

239

View full text Add to dashboard Cite

We have investigated the expression of interleukin-3 receptor ␣ (IL-3R␣) chain in primary blasts from 79 patients with acute myeloid leukemia (AML), 25 patients with B-acute lymphoid leukemia (B-ALL), and 7 patients with T-acute lymphoid leukemia (T-ALL) to evaluate a linkage between the expression of this receptor chain, blast proliferative status, and disease prognosis. Although IL-3R␣ chain was scarcely expressed in most patients with T-ALL, it was overexpressed in 40% and 45% of patients with B-ALL and AML, respectively, compared with the levels observed in normal CD34 ؉ progenitors. The biological and clinical significance of this overexpression pattern was investigated in AML. At the biological level, elevated IL-3R␣ expression was associated with peculiar properties of leukemic blasts, specifically in 3 areas. First, in all patients the blasts expressing elevated IL-3R␣ levels exhibited higher cycling activity and increased resistance to apoptosis triggered by growth factor deprivation. Second, spontaneous signal transducer and activator of transcription 5 (Stat5) phosphorylation was observed in 13% of AML patients, all pertaining to the group of patients exhibiting high IL-3R␣ expression. Third, following IL-3 treatment, Stat5 was activated at higher levels in blasts with elevated IL-3R␣ expression. At the clinical level, a significant correlation was observed between the level of IL-3R␣ expression and the number of leukemic blasts at diagnosis, and patients exhibiting elevated IL-3R␣ levels had a lower complete remission rate and survival duration than those showing normal IL-3R␣ levels. These findings suggest that in AML, deregulated expression of IL-3R␣ may contribute to the proliferative advantage of the leukemic blasts and, hence, to a poor prognosis. IntroductionBlood cells are derived from a small number of pluripotent hemopoietic stem cells (HSCs) endowed with the capacity to self-renew and to differentiate into hemopoietic progenitor cells (HPCs) progressively committed to proceed along one of the maturation pathways. 1 Survival, growth, and differentiation of HPCs are, at least in part, regulated by a network of hematopoietic growth factors (HGFs) called colony-stimulating factors (CSFs) or interleukins (ILs).Acute leukemias are characterized by an arrest of cell maturation and the accumulation of undifferentiated cells in marrow, blood, and other tissues. 2 As observed in normal hematopoiesis, most leukemic cells descend from a relatively small pool of progenitor cells with high proliferative activity. In line with this hypothesis, recent studies have shown that acute myeloid leukemia (AML) cells with the membrane phenotype CD34 ϩ Thy-1 Ϫ , 3 CD34 ϩ CD38 Ϫ , 4 or CD34 ϩ CD71 Ϫ HLA-DR Ϫ5 are capable of engrafting immunodeficient mice.Acute leukemia cells have usually retained responsiveness to HGF stimulation in the promotion of cell survival and cell proliferation; however, leukemic cells show little maturation under stimulation with HGFs. 6 More particularly, recombinant IL-3 and granulocyte...

show abstract

“…44,45 AML samples are highly heterogeneous in their need for growth factors to support both clonogenic growth 50 and survival in suspension culture. 51 In some cases of AML, growth factors may be needed to maintain pathways that protect the mitochondrial membrane from depolarization. We therefore hypothesized that samples that undergo the most spontaneous apoptosis in vitro have mitochondrial membranes that depolarize the most readily.…”

Section: Mtp Sensitivity To Mclccp In Primary Aml Blasts and Cell Linesmentioning

confidence: 99%

Mitochondrial membrane sensitivity to depolarization in acute myeloblastic leukemia is associated with spontaneous in vitro apoptosis, wild-type TP53, and vicinal thiol/disulfide status

Pallis

Grundy

Turzanski

et al. 2001

Blood

View full text Add to dashboard Cite

Nonresponse to remission-induction chemotherapy, which remains a major problem in acute myeloblastic leukemia (AML), has been linked to cellular resistance to apoptosis. Because the apoptosis induced by chemotherapeutic drugs is mediated by loss of mitochondrial transmembrane potential (MTP), it was postulated that sensitivity to mitochondrial membrane depolarization might be heterogeneous in AML. Using the uncoupling agent carbonyl cyanide m-chlorophenylhydrazone (mClCCP), the mitochondrial membrane sensitivity to depolarization

show abstract

The effects of recombinant CSF‐1 on the blast cells of acute myeloblastic leukemia in suspension culture

Cited by 76 publications

References 25 publications

Proliferative effects of several hematopoietic growth factors on acute myelogenous leukemia cells and correlation with treatment outcome

Proliferative effects of several hematopoietic growth factors on acute myelogenous leukemia cells and correlation with treatment outcome

Elevated expression of IL-3Rα in acute myelogenous leukemia is associated with enhanced blast proliferation, increased cellularity, and poor prognosis

Mitochondrial membrane sensitivity to depolarization in acute myeloblastic leukemia is associated with spontaneous in vitro apoptosis, wild-type TP53, and vicinal thiol/disulfide status

Contact Info

Product

Resources

About