Clonality of the stem cell compartment during evolution of myelodysplastic syndromes and other bone marrow failure syndromes

The myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are haematologically diverse stem cell malignancies sharing phenotypic features of both myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) that display a paradoxical bone marrow phenotype hallmarked by myeloid proliferation in the context of bone marrow dysplasia and ineffective haematopoiesis. The unfolding MDS/MPN genomic landscape has revealed numerous mutations in signalling genes, such as CBL, JAK2, NRAS, KRAS, CSF3R, and others involving the spliceosome complex. These observations suggest that comutation of genes involved in dysplasia and bone marrow failure along with those of cytokine receptor signalling may, in part, explain the dual MDS/MPN phenotype. The respective MDS/MPN diseases are identified by the type of myeloid subset which predominates in the peripheral blood. Currently there are no standard treatment recommendations for most patients with MDS/MPN. To optimize efforts to improve the management and disease outcomes, it is essential to identify meaningful clinical and biologic endpoints and standardized response criteria for clinical trials.

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Brief Report: Initial Investigations of the Changes in the Stem Cell Compartment of Murine Bone Marrow During Post-Hypoxic Polycythemia

Blood ◽

10.1182/blood.v33.6.859.859 ◽

1969 ◽

Vol 33 (6) ◽

pp. 859-864 ◽

Cited By ~ 7

Author(s):

J. M. HURST ◽

M. S. TURNER ◽

J. M. YOFFEY ◽

L. G. LAJTHA

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Cell Compartment ◽

Cell Content ◽

Murine Bone Marrow ◽

Stem Cell Compartment

Abstract As assessed by its spleen colony-forming ability, the stem cell content of bone marrow from mice recovering from hypoxia increases with the duration of erythropoietic depression, and is directly proportional to the number of marrow lymphocytes.

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Upregulation of Flt3 Expression within the Bone Marrow Lin−Sca1+c-kit+ Stem Cell Compartment Is Accompanied by Loss of Self-Renewal Capacity

Immunity ◽

10.1016/s1074-7613(01)00220-5 ◽

2001 ◽

Vol 15 (4) ◽

pp. 659-669 ◽

Cited By ~ 473

Author(s):

Jörgen Adolfsson ◽

Ole Johan Borge ◽

David Bryder ◽

Kim Theilgaard-Mönch ◽

Ingbritt Åstrand-Grundström ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Cell Compartment ◽

Self Renewal ◽

Loss Of Self ◽

Stem Cell Compartment ◽

Flt3 Expression

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Effect of stem cell factor on in vitro erythropoiesis in patients with bone marrow failure syndromes

Blood ◽

10.1182/blood.v80.12.3000.bloodjournal80123000 ◽

1992 ◽

Vol 80 (12) ◽

pp. 3000-3008

Author(s):

BP Alter ◽

ME Knobloch ◽

L He ◽

AP Gillio ◽

RJ O'Reilly ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Stem Cell Factor ◽

Mononuclear Cells ◽

Bone Marrow Failure ◽

Dyskeratosis Congenita ◽

Normal Numbers ◽

Erythroid Progenitors ◽

Bone Marrow Failure Syndromes

Stem cell factor (SCF) enhances normal hematopoiesis. We examined its effect in vitro on bone marrow and blood progenitors from patients with inherited bone marrow failure syndromes, including 17 patients each with Diamond-Blackfan anemia (DBA) and Fanconi's anemia (FA), 3 with dyskeratosis congenita (DC), and 1 each with amegakaryocytic thrombocytopenia (amega) and transient erythroblastopenia of childhood (TEC). Mononuclear cells were cultured with erythropoietin (Ep) alone or combined with SCF or other factors. SCF increased the growth of erythroid progenitors in cultures from 50% of normal controls, 90% of DBA, 70% of FA, 30% of DC, and the amega and TEC patients; normal numbers were reached in 25% of DBA studies. Improved in vitro erythropoiesis with SCF in all types of inherited marrow failure syndromes does not suggest a common defect involving kit or SCF, but implies that SCF may be helpful in the treatment of hematopoietic defects of varied etiologies.

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Stem cells in liver repair

The Biochemist ◽

10.1042/bio02801011 ◽

2006 ◽

Vol 28 (1) ◽

pp. 11-14

Author(s):

Yiannis N. Kallis ◽

Stuart J. Forbes

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Stem Cell ◽

Liver Regeneration ◽

Liver Tissue ◽

Metabolic Diseases ◽

Viral Infections ◽

Biliary Tree ◽

Cell Compartment ◽

Stem Cell Compartment

The liver can be subjected to many damaging insults, usually from toxins, viral infections, immune or metabolic diseases, during its lifetime. Normal restoration of liver tissue occurs via division of mature functional hepatocytes. In addition, a liver-stem-cell compartment, lying deep within the intrahepatic biliary tree, can be activated during severe or iterative stress. Recent studies have suggested that the bone marrow (BM) may also contribute to liver regeneration, although these observations remain controversial.

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Effect of stem cell factor on in vitro erythropoiesis in patients with bone marrow failure syndromes

Blood ◽

10.1182/blood.v80.12.3000.3000 ◽

1992 ◽

Vol 80 (12) ◽

pp. 3000-3008 ◽

Cited By ~ 31

Author(s):

BP Alter ◽

ME Knobloch ◽

L He ◽

AP Gillio ◽

RJ O'Reilly ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Stem Cell Factor ◽

Mononuclear Cells ◽

Bone Marrow Failure ◽

Dyskeratosis Congenita ◽

Normal Numbers ◽

Erythroid Progenitors ◽

Bone Marrow Failure Syndromes

Abstract Stem cell factor (SCF) enhances normal hematopoiesis. We examined its effect in vitro on bone marrow and blood progenitors from patients with inherited bone marrow failure syndromes, including 17 patients each with Diamond-Blackfan anemia (DBA) and Fanconi's anemia (FA), 3 with dyskeratosis congenita (DC), and 1 each with amegakaryocytic thrombocytopenia (amega) and transient erythroblastopenia of childhood (TEC). Mononuclear cells were cultured with erythropoietin (Ep) alone or combined with SCF or other factors. SCF increased the growth of erythroid progenitors in cultures from 50% of normal controls, 90% of DBA, 70% of FA, 30% of DC, and the amega and TEC patients; normal numbers were reached in 25% of DBA studies. Improved in vitro erythropoiesis with SCF in all types of inherited marrow failure syndromes does not suggest a common defect involving kit or SCF, but implies that SCF may be helpful in the treatment of hematopoietic defects of varied etiologies.

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