Possible Juvenile Myelocytic leukaemia in a child with NF1 – an underlying stem cell defect?

2019 ◽  
Author(s):  
Callum Fernando ◽  
Anne Kelly
Keyword(s):  
Stem Cell ◽  
Myelocytic Leukaemia ◽  
Cell Defect

Stem Cell Defect in Ubiquitin-Green Fluorescent Protein Mice Facilitates Engraftment of Lymphoid-Primed Hematopoietic Stem Cells

Stem Cells ◽  
2018 ◽  
Vol 36 (8) ◽  
pp. 1237-1248
Author(s):  
Kateřina Faltusová ◽  
Katarína Szikszai ◽  
Martin Molík ◽  
Jana Linhartová ◽  
Petr Páral ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Green Fluorescent Protein ◽  
Hematopoietic Stem Cells ◽  
Fluorescent Protein ◽  
Hematopoietic Stem ◽  
Green Fluorescent ◽  
Cell Defect

scholarly journals Incomplete restoration of Mpl expression in the mpl−/− mouse produces partial correction of the stem cell–repopulating defect and paradoxical thrombocytosis

Blood ◽  
2009 ◽  
Vol 113 (8) ◽  
pp. 1778-1785 ◽  
Author(s):  
Brian J. Lannutti ◽  
Angela Epp ◽  
Jacqueline Roy ◽  
Junmei Chen ◽  
Neil C. Josephson
Keyword(s):  
Stem Cell ◽  
Elevated Plasma ◽  
Platelet Production ◽  
Ectopic Gene Expression ◽  
Unexpected Consequence ◽  
Kinase Phosphorylation ◽  
Bone Marrow Chimeras ◽  
Partial Correction ◽  
Cell Defect ◽  
Expression And Activity

Abstract Expression of Mpl is restricted to hematopoietic cells in the megakaryocyte lineage and to undifferentiated progenitors, where it initiates critical cell survival and proliferation signals after stimulation by its ligand, thrombopoietin (TPO). As a result, a deficiency in Mpl function in patients with congenital amegakaryocytic thrombocytopenia (CAMT) and in mpl−/− mice produces profound thrombocytopenia and a severe stem cell–repopulating defect. Gene therapy has the potential to correct the hematopoietic defects of CAMT by ectopic gene expression that restores normal Mpl receptor activity. We rescued the mpl−/− mouse with a transgenic vector expressing mpl from the promoter elements of the 2-kb region of DNA just proximal to the natural gene start site. Transgene rescued mice exhibit thrombocytosis but only partial correction of the stem cell defect. Furthermore, they show very low-level expression of Mpl on platelets and megakaryocytes, and the transgene-rescued megakaryocytes exhibit diminished TPO-dependent kinase phosphorylation and reduced platelet production in bone marrow chimeras. Thrombocytosis is an unexpected consequence of reduced Mpl expression and activity. However, impaired TPO homeostasis in the transgene-rescued mice produces elevated plasma TPO levels, which serves as an unchecked stimulus to drive the observed excessive megakaryocytopoiesis.

scholarly journals Effect of a congenital defect in hemopoiesis on myeloid growth and the stem cell (CFU) in an in vivo culture system

Blood ◽  
1976 ◽  
Vol 47 (3) ◽  
pp. 413-421 ◽  
Author(s):  
WS Tyler ◽  
F Jr Stohlman ◽  
M Chovaniec ◽  
D Howard
Keyword(s):  
Stem Cell ◽  
Culture System ◽  
Control Level ◽  
Spillover Effect ◽  
Diffusion Chamber ◽  
Defect Diffusion ◽  
In Vivo Culture ◽  
Cell Defect ◽  
Humoral Control

Abstract W/Wv mice with congenitally defective CFU proliferation and their normal, congenic littermates were used as hosts for diffusion chamber (DC) implants. CFU growth in implanted allogenic CF1, or congenic +/+ marrow was significantly greater in W/Wv than in control hosts. When W/Wv mice were “cured” of their hemopoietic defect, CFU proliferation in the DCs decreased, but not to the control level. These observations have provided evidence for humoral control of CFU growth related to a genetic stem cell defect. Diffusion chamber myelopoiesis was also enhanced in W/Wv hosts. In comparison with their congenic controls, W/Wv mice were neutropenic and had decreased numbers of marrow myeloid elements. Thus, a humorally mediated feedback related to a defective myelopoiesis in the hosts might have accounted for increased DC myelopoiesis. However, a “spillover”effect from increased stem cell growth has not been excluded.

Stem cell defect in aplastic anemia

1999 ◽  
pp. 3-20 ◽  
Author(s):  
Judith C.W. Marsh ◽  
Nydia G. Testa
Keyword(s):  
Stem Cell ◽  
Aplastic Anemia ◽  
Cell Defect

scholarly journals Salt sensitive hypertension associated with stem cell defect in the renal medulla of Dahl S rats

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Zhengchao Wang ◽  
Min Xia ◽  
Qing Zhu ◽  
Pin‐Lan Li ◽  
Ningjun Li
Keyword(s):  
Stem Cell ◽  
Renal Medulla ◽  
Salt Sensitive Hypertension ◽  
Cell Defect

Stem cell defect in aplastic anemia: reduced long term culture-initiating cells (LTC-IC) in CD34+ cells isolated from aplastic anemia patient bone marrow

2002 ◽  
Vol 3 (5) ◽  
pp. 230-236 ◽  
Author(s):  
Sian Rizzo ◽  
John Scopes ◽  
Modupe O Elebute ◽  
Helen A Papadaki ◽  
Edward C Gordon-Smith ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Aplastic Anemia ◽  
Long Term Culture ◽  
Aplastic Anemia Patient ◽  
Cd34 Cells ◽  
Anemia Patient ◽  
Cell Defect

Prognostic importance of immunophenotyping in adults with acute myelocytic leukaemia: the significance of the stem-cell glycoprotein CD34 (My 10)

1990 ◽  
Vol 76 (3) ◽  
pp. 340-347 ◽  
Author(s):  
Robert B. Geller ◽  
Marianna Zahurak ◽  
Craig A. Hurwitz ◽  
Philip J. Burke ◽  
Judith E. Karp ◽  
...  
Keyword(s):  
Stem Cell ◽  
Myelocytic Leukaemia ◽  
Prognostic Importance ◽  
Acute Myelocytic Leukaemia

Clonal hematopoiesis in familial polycythemia vera suggests the involvement of multiple mutational events in the early pathogenesis of the disease

Blood ◽  
2003 ◽  
Vol 102 (10) ◽  
pp. 3793-3796 ◽  
Author(s):  
Robert Kralovics ◽  
David W. Stockton ◽  
Josef T. Prchal
Keyword(s):  
Stem Cell ◽  
Polycythemia Vera ◽  
Cell Clone ◽  
Incomplete Penetrance ◽  
Erythroid Progenitors ◽  
Familial Predisposition ◽  
Clonal Hematopoiesis ◽  
Healthy Family ◽  
Cell Defect ◽  
Autosomal Dominant Inheritance Pattern

AbstractFamilial clustering of malignancies provides a unique opportunity to identify molecular causes of cancer. Polycythemia vera (PV) is a myeloproliferative disorder due to an unknown somatic stem cell defect that leads to clonal myeloid hyperproliferation. We studied 6 families with PV. The familial predisposition to PV appears to follow an autosomal dominant inheritance pattern with incomplete penetrance. All examined females informative for a transcriptional clonality assay had clonal hematopoiesis. We excluded linkage between PV and a number of previously proposed candidate disease loci (c-mpl, EPOR, 20q, 13q, 5q, 9p). Therefore, mutations at these loci are unlikely primary causes of familial PV. The finding of erythropoietin-independent erythroid progenitors in healthy family members indicated the presence of the PV stem cell clone in their hematopoiesis. This finding, together with clonal hematopoiesis in the affected individuals, supports the hypothesis of multiple genetic defects involved in the early pathogenesis of PV. (Blood. 2003;102:3793-3796)

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