Clonal origin of chronic myelocytic leukemia in man.

Fialkow, Philip J.; Gartler, Stanley M.; Yoshida, Akira

doi:10.1073/pnas.58.4.1468

Cited by 479 publications

(208 citation statements)

References 10 publications

Supporting

Mentioning

197

Contrasting

Unclassified

Order By: Relevance

“…4,5 This constituted the first direct evidence that CML is a clonal disorder, in addition to cementing the idea advanced by Dameshek that the clone originates in a normal HSC. 1 Studies of X-chromosome inactivation patterns in CML patients' cells subsequently confirmed the leukemic origin of the expanded granulomonocytic 6,7 compartment, as well as all of the circulating red blood cells, platelets and some B cells, but not T cells, in these patients. [6][7][8] Ultimately, recognition of the unique specificity of the BCR-ABL gene rearrangement in individual patients' cells provided the final definitive evidence that chronic phase CML is a multi-lineage clonal disease and the retrospective inference that it originates from a normal multipotent hematopoietic cell with long-term self-sustaining properties.…”

mentioning

confidence: 94%

Insights into the stem cells of chronic myeloid leukemia

et al. 2010

View full text Add to dashboard Cite

Chronic myeloid leukemia (CML) has long served as a paradigm for generating new insights into the cellular origin, pathogenesis and improved approaches to treating many types of human cancer. Early studies of the cellular phenotypes and genotypes represented in leukemic populations obtained from CML patients established the concept of an evolving clonal disorder originating in and initially sustained by a rare, multipotent, self-maintaining hematopoietic stem cell (HSC). More recent investigations continue to support this model, while also revealing new insights into the cellular and molecular mechanisms that explain how knowledge of CML stem cells and their early differentiating progeny can predict the differing and variable features of chronic phase and blast crisis. In particular, these emphasize the need for new agents that effectively and specifically target CML stem cells to produce non-toxic, but curative therapies that do not require lifelong treatments.

show abstract

mentioning

confidence: 94%

Insights into the stem cells of chronic myeloid leukemia

et al. 2010

View full text Add to dashboard Cite

show abstract

“…1 The first clonality studies performed to investigate the nature of human neoplasms were done almost three decades ago, [2][3][4] and have opened a fertile field of investigation that has allowed investigators to unravel some of the basic tenets of modern oncology. The current decade has been particularly prolific with the largest number of clonality studies performed yet, and the accumulation of an unprecedented quantity of data.…”

Section: Introductionmentioning

confidence: 99%

X-inactivation analysis in the 1990s: promise and potential problems

Busque

Gilliland

1998

Leukemia

View full text Add to dashboard Cite

“…In BCR-ABL induced CML, LSCs phenotypically appear to be similar to the normal hematopoietic stem cells (HSC). Fialkow and colleagues examined different cell types in chronic phase CML patients for the presence of the Ph chromosome (Fialkow et al, 1967(Fialkow et al, , 1977. Surprisingly, both granulocytes and erythroid cells from chronic phase CML patients contained the Ph chromosome, even though only myeloid cells are expanded during chronic phase CML.…”

Section: Bcr-abl Kinase Inhibitor and CML Stem Cellsmentioning

confidence: 99%

Molecular and cellular bases of chronic myeloid leukemia

Chen¹,

Peng²,

Li³

et al. 2010

Protein Cell

View full text Add to dashboard Cite

Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by the overproduction of granulocytes, which leads to high white blood cell counts and splenomegaly in patients. Based on clinical symptoms and laboratory findings, CML is classified into three clinical phases, often starting with a chronic phase, progressing to an accelerated phase and ultimately ending in a terminal phase called blast crisis. Blast crisis phase of CML is clinically similar to an acute leukemia; in particular, B-cell acute lymphoblastic leukemia (B-ALL) is a severe form of acute leukemia in blast crisis, and there is no effective therapy for it yet. CML is induced by the BCR-ABL oncogene, whose gene product is a BCR-ABL tyrosine kinase. Currently, inhibition of BCR-ABL kinase activity by its kinase inhibitor such as imatinib mesylate (Gleevec) is a major therapeutic strategy for CML. However, the inability of BCR-ABL kinase inhibitors to completely kill leukemia stem cells (LSCs) indicates that these kinase inhibitors are unlikely to cure CML. In addition, drug resistance due to the development of BCR-ABL mutations occurs before and during treatment of CML with kinase inhibitors. A critical issue to resolve this problem is to fully understand the biology of LSCs, and to identify key genes that play significant roles in survival and self-renewal of LSCs. In this review, we will focus on LSCs in CML by summarizing and discussing available experimental results, including the original studies from our own laboratory.

show abstract

Clonal origin of chronic myelocytic leukemia in man.

Cited by 479 publications

References 10 publications

Insights into the stem cells of chronic myeloid leukemia

Insights into the stem cells of chronic myeloid leukemia

X-inactivation analysis in the 1990s: promise and potential problems

Molecular and cellular bases of chronic myeloid leukemia

Contact Info

Product

Resources

About