Granulopoiesis in Chronic Granulocytic Leukaemia*

Galbraith, Peter R.; Abu-Zahra, Hakam

doi:10.1111/j.1365-2141.1972.tb08795.x

Cited by 46 publications

(10 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During the chronic phase of CML, an expansion of the leukemic cells occurs which leads to an approximately 5 ± 10-fold increase in total hematopoietic cell mass (Clarkson and Strife, 1993). While these cells do not have an increased proliferative rate, they do undergo extra cell divisions and have longer survival times than normal myeloid progenitors (Athens et al, 1965;Chervenick and Boggs, 1968;Clarkson and Strife, 1993;Galbraith and Abu-Zahra, 1972;Goto et al, 1982;Ogawa et al, 1970;Scott et al, 1971;Strife and Clarkson, 1988;Stryokmans et al, 1977). Mitogenic signals from Bcr-Abl may serve to inhibit cell cycle exit that would normally occur during the dierentiation process.…”

Section: Discussionmentioning

confidence: 99%

The Bcr-Abl tyrosine kinase activates mitogenic signaling pathways and stimulates G1-to-S phase transition in hematopoietic cells

1997

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

The Bcr-Abl tyrosine kinase activates mitogenic signaling pathways and stimulates G1-to-S phase transition in hematopoietic cells

1997

View full text Add to dashboard Cite

“…324,422,424,425 The rates of cell production are similar in the marrow and spleen, and in patients with massive splenic involvement, the majority of circulating immature granulocytes may originate in the spleen. 324,430 Leukocyte kinetic studies [431][432][433][434][435] have shown that the size of the total blood granulocyte pool in CML patients may be 10-100 times greater than normal; both the circulating granulocyte pool (CGP) and marginated granulocyte pool are grossly expanded.…”

Section: Cell Cycle and Other Kinetic Parametersmentioning

confidence: 99%

Chronic myelogenous leukemia as a paradigm of early cancer and possible curative strategies

et al. 2003

View full text Add to dashboard Cite

The chronological history of the important discoveries leading to our present understanding of the essential clinical, biological, biochemical, and molecular features of chronic myelogenous leukemia (CML) are first reviewed, focusing in particular on abnormalities that are responsible for the massive myeloid expansion. CML is an excellent target for the development of selective treatment because of its highly consistent genetic abnormality and qualitatively different fusion gene product, p210(bcr-abl). It is likely that the multiple signaling pathways dysregulated by p210(bcr-abl) are sufficient to explain all the initial manifestations of the chronic phase of the disease, although understanding of the circuitry is still very incomplete. Evidence is presented that the signaling pathways that are constitutively activated in CML stem cells and primitive progenitors cooperate with cytokines to increase the proportion of stem cells that are activated and thereby increase recruitment into the committed progenitor cell pool, and that this increased activation is probably the primary cause of the massive myeloid expansion in CML. The cooperative interactions between Bcr-Abl and cytokine-activated pathways interfere with the synergistic interactions between multiple cytokines that are normally required for the activation of stem cells, while at the same time causing numerous subtle biochemical and functional abnormalities in the later progenitors and precursor cells. The committed CML progenitors have discordant maturation and reduced proliferative capacity compared to normal committed progenitors, and like them, are destined to die after a limited number of divisions. Thus, the primary goal of any curative strategy must be to eliminate all Philadelphia positive (Ph+) primitive cells that are capable of symmetric division and thereby able to expand the Ph+ stem cell pool and recreate the disease. Several highly potent and moderately selective inhibitors of Bcr-Abl kinase have recently been discovered that are capable of killing the majority of actively proliferating early CML progenitors with minimal effects on normal progenitors. However, like their normal counterparts, most of the CML primitive stem cells are quiescent at any given time and are relatively invulnerable to the Bcr-Abl kinase inhibitors as well as other drugs. We propose that survival of dormant Ph+ stem cells may be the most important reason for the inability to cure the disease during initial treatment, while resistance to the inhibitors and other drugs becomes increasingly important later. An outline of a possible curative strategy is presented that attempts to take advantage of the subtle differences in the proliferative behavior of normal and Ph+ stem cells and the newly discovered selective inhibitors of Bcr-Abl. Leukemia (2003) 17, 1211-1262. doi:10.1038/sj.leu.2402912

show abstract

“…Chronic myeloid leukaemia (CML) is a clonal, pluoripotent stem cell disorder characterized by the occurrence of Philadelphia chromosome (Ph 1 ) and presence of a large number of mature and immature myeloid cells in the peripheral blood [7]. Earlier work from our laboratory has shown that PMNL from CML patients were defective in actin dependent functions such as chemotaxis, degranulation, endocytosis, etc.…”

Section: Introductionmentioning

confidence: 99%

Altered Ca2+ homeostasis in polymorphonuclear leukocytes from chronic myeloid leukaemia patients

2006

View full text Add to dashboard Cite

Background: In polymorphonuclear leukocytes (PMNL), mobilization of calcium ions is one of the early events triggered by binding of chemoattractant to its receptors. Besides chemotaxis, a variety of other functional responses are dependent on calcium ion mobilization. PMNL from chronic myeloid leukaemia (CML) patients that were morphologically indistinguishable from normal PMNL were found to be defective in various functions stimulated by a chemoattractant -fMLP. To study the mechanism underlying defective functions in CML PMNL, we studied calcium mobilization in CML PMNL in response to two different classical chemoattractants, fMLP and C5a.

show abstract

Granulopoiesis in Chronic Granulocytic Leukaemia*

Cited by 46 publications

References 10 publications

The Bcr-Abl tyrosine kinase activates mitogenic signaling pathways and stimulates G1-to-S phase transition in hematopoietic cells

The Bcr-Abl tyrosine kinase activates mitogenic signaling pathways and stimulates G1-to-S phase transition in hematopoietic cells

Chronic myelogenous leukemia as a paradigm of early cancer and possible curative strategies

Altered Ca2+ homeostasis in polymorphonuclear leukocytes from chronic myeloid leukaemia patients

Contact Info

Product

Resources

About