scholarly journals Hematopoietic Stem Cells in Chronic Myeloid Leukemia

10.5772/54651 ◽  
2013 ◽  
Author(s):  
Antonieta Chvez-Gonzlez ◽  
Scrates Avils-Vzquez ◽  
Dafne Moreno Lorenzana ◽  
Hctor Mayani
Keyword(s):  
Stem Cells ◽  
Chronic Myeloid Leukemia ◽  
Hematopoietic Stem Cells ◽  
Myeloid Leukemia ◽  
Hematopoietic Stem

scholarly journals Characterization of stage progression in chronic myeloid leukemia by DNA microarray with purified hematopoietic stem cells

Oncogene ◽  
2001 ◽  
Vol 20 (57) ◽  
pp. 8249-8257 ◽  
Author(s):  
Ken Ohmine ◽  
Jun Ota ◽  
Masuzu Ueda ◽  
Shu-ichi Ueno ◽  
Koji Yoshida ◽  
...  
Keyword(s):  
Stem Cells ◽  
Chronic Myeloid Leukemia ◽  
Hematopoietic Stem Cells ◽  
Dna Microarray ◽  
Myeloid Leukemia ◽  
Hematopoietic Stem ◽  
Stage Progression

Plasmacytoid Dendritic Cells Derived from Chronic Myeloid Leukemia Induced by Low Dose Cytosine Arabinoside Combined with Flt-3L and TPO

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4918-4918
Author(s):  
Lijuan Li ◽  
Lian- Sheng Zhang
Keyword(s):  
Stem Cells ◽  
Dendritic Cells ◽  
Chronic Myeloid Leukemia ◽  
Influenza Vaccine ◽  
Hematopoietic Stem Cells ◽  
Cytosine Arabinoside ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Control Group ◽  
Hematopoietic Stem

Abstract Objective Plasmacytoid dendritic cells(pDC) as a subtype of dendritic cells, play an important immunological effects in the body.It is a focus in resent research. After stimulated by viruses or CpG ODNs, pDC produce large amounts of IFN-α rapidly, result in an strong non-specific immunological effect, and then become differentiation and maturation, and attained certain antigen presenting function in adaptive immune response, act as a bridge connecting innate immunity with adaptive immunity. In vitro, FLT-3L combination with TPO can successfully develop pDC from hematopoietic stem cells. Chronic myeloid leukemia(CML) is a hematopoietic stem cell malignant proliferation of the disease. There are series of immune abnormalities in patients with CML. It is well known that Interferon - α treatment of CML is effective, patients can be gained part of cytogenetic and molecular biology mitigation, and effective in patients with interferon therapy, the long-term prognosis is superior to other methods of treatment. Clinical experience also found that low dose cytosine arabinoside(LD-Ara-C) in combination with interferon is superior therapeutic effect of interferon treatment alone. We assumed that whether the LD-Ara-C in patients has an improvement in the immune dysfunction? Whether it will affect on CML-derived pDC differentiation, maturation and function? Therefore, we used LD-Ara-C joint FLT-3L, TPO cultivante CML-derived hematopoietic stem cells that make it differentiate into CML derived pDC to study LD-Ara-C for the treatment of CML may be immune mechanism for the clinical treatment theory. Method Bone marrow mononuclear cells (BMMNCs) were isolated from CML patients in chronic phase at diagnosis by density gradient centrifugation. BMMNCs were incubate with a cocktail of Flt-3 and TPO, Ara-C were added at the same time of 5ng/ml (A1), 10ng/ml (A2), 25ng/ml (A3), 50ng/ml (A4) and zero as the control, respectively. After 30 days of culture, the morphologic features were observed and CD4,CD11c, CD123, BDCA-2 were analyzed by flow cytometry, IFN-α concentration in supernate were detected by ELISA kits after added influenza vaccine. Results after 25d of culture, cells clustered with increased size and widespread cytoplasmic projection. Wright-Giemsa-stained cytospin preparation the pDC displays an eccentric kidney-shaped nucleus.The immunophenotype expression of CD4,CD123 and BDCA-2 on pDCs of group A1 and A2 were obviously higher than control group(p<0.05),and group A1 were higher than A2(p<0.05). The majority cells of group A3 and all cells of A4 were died. The group A1 had the highest level of the secretion of IFN-α than A2 and than control group(p<0.05) Conclusion LD-Ara-C in combination with Flt-3 and TPO can induce CML cells into pDCs which express the typical immunophenotype, Increase the production of IFN-α on stimulated by influenza vaccine. This study indicates that LD-Ara-C increase the quantity of pDC and IFN-α production, and this maybe explain why the therapy with LD-Ara-C in CML patients have better outcome.

scholarly journals BCR-ABL enhances differentiation of long-term repopulating hematopoietic stem cells

Blood ◽  
2010 ◽  
Vol 115 (16) ◽  
pp. 3185-3195 ◽  
Author(s):  
Mirle Schemionek ◽  
Christian Elling ◽  
Ulrich Steidl ◽  
Nicole Bäumer ◽  
Ashley Hamilton ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Hematopoietic Stem Cells ◽  
Progenitor Cells ◽  
Myeloid Leukemia ◽  
Bone Marrow Cells ◽  
Hematopoietic Stem ◽  
Multipotent Progenitor Cells

Abstract In a previously developed inducible transgenic mouse model of chronic myeloid leukemia, we now demonstrate that the disease is transplantable using BCR-ABL+ Lin−Sca-1+c-kit+ (LSK) cells. Interestingly, the phenotype is more severe when unfractionated bone marrow cells are transplanted, yet neither progenitor cells (Lin−Sca-1−c-kit+), nor mature granulocytes (CD11b+Gr-1+), nor potential stem cell niche cells (CD45−Ter119−) are able to transmit the disease or alter the phenotype. The phenotype is largely independent of BCR-ABL priming before transplantation. However, prolonged BCR-ABL expression abrogates the potential of LSK cells to induce full-blown disease in secondary recipients and increases the fraction of multipotent progenitor cells at the expense of long-term hematopoietic stem cells (LT-HSCs) in the bone marrow. BCR-ABL alters the expression of genes involved in proliferation, survival, and hematopoietic development, probably contributing to the reduced LT-HSC frequency within BCR-ABL+ LSK cells. Reversion of BCR-ABL, or treatment with imatinib, eradicates mature cells, whereas leukemic stem cells persist, giving rise to relapsed chronic myeloid leukemia on reinduction of BCR-ABL, or imatinib withdrawal. Our results suggest that BCR-ABL induces differentiation of LT-HSCs and decreases their self-renewal capacity.

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