Can bone marrow cellularity help in predicting prognosis in myelodysplastic syndromes?

2018 ◽  
Vol 101 (4) ◽  
pp. 502-507 ◽  
Author(s):  
Uri Greenbaum ◽  
Erel Joffe ◽  
Kalman Filanovsky ◽  
Howard S. Oster ◽  
Ilya Kirgner ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndromes ◽  
Bone Marrow Cellularity ◽  
Marrow Cellularity

scholarly journals Aberrant Hematopoietic Stem Cell Function in Mice Haploinsufficient for a 2 Mb Deletion of Chromosome 5A3 Syntenic to a Region of Human 7q22 Frequently Deleted in Myelodysplastic Syndromes

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3247-3247
Author(s):  
Jasmine C. Wong ◽  
Kelley Weinfurtner ◽  
Pilar Alzamora ◽  
Scott C. Kogan ◽  
Michael R. Burgess ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Myelodysplastic Syndromes ◽  
Hematopoietic Cells ◽  
Chromosome 7 ◽  
Chromosome Band ◽  
Hematopoietic Stem ◽  
Bone Marrow Cellularity ◽  
Marrow Cellularity

Abstract The myelodysplastic syndromes (MDS) are clonal hematologic neoplasms characterized by normal, increased or decreased bone marrow cellularity, ineffective production of one or more blood cell lineages, morphologic dysplasia, and a variable risk of progression to acute myeloid leukemia. Somatic monosomy 7 (-7) and deletions affecting the long arm of chromosome 7 [del(7q)] are highly prevalent cytogenetic abnormalities in de novo and therapy-related MDS that are associated with advanced age, prior exposure to alkylating agents, a high risk of leukemic transformation, and intrinsic drug resistance. Although recent genome-wide and targeted DNA sequencing efforts have uncovered mutations in genes involved in chromatin modification, transcription, RNA splicing, and signal transduction in MDS, extensive sequencing and expression analysis have not revealed recurring “second hit” mutations of any gene located on chromosome band 7q22, which is commonly deleted in patients with myeloid malignancies. Therefore, answering the long-standing question of how recurrent deletions of the long arm of chromosome 7 contribute to initiation, maintenance, and clinical outcome of MDS remains a fundamental challenge. Given the importance of understanding the biology of -7/del(7q) and the urgent need to develop new mechanism-based treatments for hematologic cancers with these deletions, we generated mice with a heterozygous germline deletion of a 2 Mb interval of chromosome band 5A3 syntenic to an interval of human chromosome band 7q22 commonly deleted in human patients (Blood 88:1930,1996). We find that 5A3 haploinsufficiency perturbs hematopoietic stem cell (HSC) development and function in vivo. 5A3+/del mice exhibit a reduced bone marrow cellularity, an expanded proportion of long-term HSCs, and an altered distribution of lineage-committed progenitors. 5A3+/del HSCs display impaired competitive reconstitution of lymphoid hematopoietic cells and a myeloid output bias, but also paradoxically show enhanced stem cell reconstitution upon aging and after serial transplantation. These defects are cell autonomous. Like WT HSCs, 5A3+/del HSCs exhaust their self-renewal potential by the tertiary round of transplantation. Taqman quantitative real-time PCR confirmed that all seven genes within the deleted interval that are expressed at detectable levels in HSC and multi-potent progenitors (MPP)(Mll5, Armc10, Psmc2, Dnajc2, Orc5l, Pmpcb and Napepld) showed ~50% reduction in transcripts in 5A3+/delHSC and MPP. Transcriptome sequencing (RNA-seq) analysis identified broad changes in lineage signature gene expression, as well as down-regulation of genes and pathways involved in oxidative phosphorylation (OXPHOS) in 5A3+/del HSCs. Whereas reactive oxygen species (ROS) are increased in aged 5A3+/del MPP, treatment of 5A3+/delmice with antioxidant N-Acetyl Cysteine failed to correct the HSC defects, suggesting that increased ROS is not the primary cause of these hematopoietic defects. Together, the abnormal properties of 5A3+/del hematopoietic cells support a mechanistic role of 7q22 deletions as contributing to cardinal features of MDS, which include impaired differentiation, myeloid lineage output bias, and a pronounced age-associated increase in disease incidence. Disclosures No relevant conflicts of interest to declare.

Prognostic significance of bone marrow cellularity in myelodysplastic syndromes: a retrospective analysis.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e18550-e18550
Author(s):  
Kiyomi Morita ◽  
Abdullah Ali ◽  
Diego Coutinho ◽  
Muhammad Umair Mushtaq ◽  
Azra Raza
Keyword(s):  
Bone Marrow ◽  
Retrospective Analysis ◽  
Myelodysplastic Syndromes ◽  
Prognostic Significance ◽  
Bone Marrow Cellularity ◽  
Marrow Cellularity

P-4 Prognostic impact of bone marrow cellularity in myelodysplastic syndromes on overall survival

2005 ◽  
Vol 29 ◽  
pp. S26
Author(s):  
S. Knipp ◽  
P. Reinecke ◽  
S. Braunstein ◽  
R. Haas ◽  
N. Gattermann ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Myelodysplastic Syndromes ◽  
Prognostic Impact ◽  
Bone Marrow Cellularity ◽  
Marrow Cellularity

Does Bone Marrow Cellularity (BMC) Have a Role in Predicting Prognosis and Survival in Myelodysplastic Syndromes (MDS)?

2017 ◽  
Vol 55 ◽  
pp. S142
Author(s):  
U. Greenbaum ◽  
E. Joffe ◽  
H.S. Oster ◽  
I. Kirgner ◽  
I. Levi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndromes ◽  
Bone Marrow Cellularity ◽  
Marrow Cellularity

scholarly journals Erratum

2018 ◽  
Vol 46 (6) ◽  
pp. 722-722
Keyword(s):  
Bone Marrow ◽  
Image Analysis ◽  
Automated Image Analysis ◽  
Proof Of Concept ◽  
Analysis Method ◽  
Image Analysis Method ◽  
Bone Marrow Cellularity ◽  
Marrow Cellularity ◽  
Rat Bone

Kozlowski, C., Brumm, J., and Cain, G. (2018). An Automated Image Analysis Method to Quantify Veterinary Bone Marrow Cellularity on H&E Sections. Tox Path46, 324–335. (Original DOI: 10.1177/0192623318766457). Kozlowski, C., Fullerton, A., Cain, G., Katavolos, P., Bravo, J., and Tarrant, J. M. (2018). Proof of Concept for an Automated Image Analysis Method to Quantify Rat Bone Marrow Hematopoietic Lineages on H&E Sections. Tox Path46, 336–347. (Oringinal DOI: 10.1177/0192623318766458). In the print issue and initial version of the online issue, the figures for Kozlowski, Brumm, and Cain were mistakenly placed into Kozlowski, Fullerton, et al., and vice versa. The online versions of both articles have been updated to display the appropriate figures.

scholarly journals STI571 (Imatinib Mesylate) Reduces Bone Marrow Cellularity and Normalizes Morphologic Features Irrespective of Cytogenetic Response

2002 ◽  
Vol 117 (3) ◽  
pp. 360-367 ◽  
Author(s):  
Robert P. Hasserjian ◽  
Federica Boecklin ◽  
Sally Parker ◽  
Andy Chase ◽  
Sunanda Dhar ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Imatinib Mesylate ◽  
Cytogenetic Response ◽  
Bone Marrow Cellularity ◽  
Marrow Cellularity

scholarly journals Qnantitation of Femoral Bone Marrow Cellularity of Rats with Acute Chloroleukemia

Blood ◽  
1965 ◽  
Vol 26 (3) ◽  
pp. 309-316 ◽  
Author(s):  
EVELYN E. VARSA ◽  
EUGENE S. HANDLER ◽  
ALBERT S. GORDON
Keyword(s):  
Bone Marrow ◽  
Leukemic Cells ◽  
Femoral Bone ◽  
Progressive Decrease ◽  
Cell Numbers ◽  
Bone Marrow Cellularity ◽  
Acute Form ◽  
Long Evans ◽  
Marrow Cellularity ◽  
Femoral Bone Marrow

Abstract Procedures of bone marrow quantitation have been applied to the study of the pathogenesis of a leukemia in rats. Mature Long-Evans rats developed an acute form of the Shay Chloroleukemia after intravenous administration of leukemic cells. Assessment of total nucleated cell numbers (normal and leukemic) per mg. of femoral bone marrow was made during the course of the pathogenesis (20 days). Reductions in the numbers of normal marrow elements were observed prior to significant increases in chloroleukemic cells. A progressive decrease in total marrow cellularity was noted in all subsequent stages. In animals surviving 17-20 days, the total number of hemic cells in the femoral marrow was found to be approximately 40 per cent of that seen in normal animals. The leukemia developed more rapidly in young than in adult animals. Using total and differential bone marrow cellularity as a criterion for the stage of pathogenesis, standardized leukemic rats can be prepared for experimentation.

Low doses of monocrotaline in rats cause diminished bone marrow cellularity and compromised nitric oxide production by peritoneal macrophages

2009 ◽  
Vol 6 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Isis M. Hueza ◽  
Julia C. Benassi ◽  
Paulo C. F. Raspantini ◽  
Leonila E. R. Raspantini ◽  
Lilian R. M. Sa´ ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Bone Marrow ◽  
Peritoneal Macrophages ◽  
Nitric Oxide Production ◽  
Low Doses ◽  
Bone Marrow Cellularity ◽  
Oxide Production ◽  
Marrow Cellularity

Bone marrow cellularity MRI calculation and correlation with bone marrow biopsy

2016 ◽  
Vol 40 (3) ◽  
pp. 392-397 ◽  
Author(s):  
George R. Matcuk ◽  
Imran Siddiqi ◽  
Steven Cen ◽  
Ashley Hagiya ◽  
Reese Isaacson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Biopsy ◽  
Bone Marrow Cellularity ◽  
Marrow Cellularity

Hmgb3 Deficiency Inhibits Down-Regulation of c-kit in Hematopoietic Stem Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 372-372
Author(s):  
Michael J. Nemeth ◽  
Stacie M. Anderson ◽  
Lisa J. Garrett-Beal ◽  
David M. Bodine
Keyword(s):  
Bone Marrow ◽  
Hind Limb ◽  
Bone Marrow Cells ◽  
Es Cells ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Bone Marrow Cellularity ◽  
Marrow Cellularity ◽  
Marrow Cells

Abstract Hmgb3 is an X-linked member of a family of sequence-independent chromatin-binding proteins that is expressed in HSC-enriched lin−, c-kitHI, Sca-1HI, IL-7Rα− (KSIL) cells and Ter119+ erythroid cells. To define Hmgb3 function, we generated hemizygous mice (Hmgb3−/Y) using 129/SvJ ES cells. Hmgb3−/Y mice contain normal numbers of KSIL cells that are capable of normal repopulation and self-renewal. However, these mice have 1.6-fold fewer common lymphoid progenitors (CLP) and 3-fold fewer common myeloid progenitors (CMP) (p < 0.05). We hypothesized that the role of Hmgb3 in early hematopoiesis involves c-kit regulation. We observed that the level of c-kit mRNA in Hmgb3−/Y HSCs increased 30% compared to wild-type (WT) (p = 0.05). We used 5-fluorouracil (5-FU), which has been shown to down-regulate c-kit on HSCs, to characterize the interaction between Hmgb3 and c-kit. We monitored Hmgb3 expression in KSIL and lin−, Sca-1+, c-kit− cells before and after 5-FU treatment (150 mg/kg) using phenotypically normal transgenic mice containing an IRES-GFP cassette knocked into the 3′ UTR of Hmgb3. Prior to 5-FU treatment, 27% of KSIL cells were GFP+ (these cells were absent 4 days post-injection {p.i.}). In contrast, 1.8% of lin−, c-kit−, Sca-1+ cells were GFP+ before 5-FU treatment whereas 26% of lin−, c-kit−, Sca-1+ cells were GFP+ 4 days p.i. The increased proportion of GFP+ lin-, c-kit−, Sca-1+ cells after 5-FU treatment is consistent with previous findings that repopulating activity resides within the c-kit−/LO population in 5-FU treated bone marrow and our finding that Hmgb3 serves as a marker for long-term repopulating activity. To determine the time course of c-kit regulation, we compared bone marrow from 5-FU injected Hmgb3−/Y and WT mice for analysis at 2, 4, and 6 days p.i. Two days p.i., both WT and Hmgb3−/Y mice contained similar numbers of bone marrow cells (7 x 106 cells/hind limb) and the KSIL population was absent. By four days p.i., the bone marrow cellularity of WT mice declined to 5.5 ± 0.9 x 106 cells/hind limb and KSIL cells were still absent. However, in Hmgb3−/Y mice 4 days p.i., bone marrow cellularity stabilized at 7.9 ± 0.8 x 106 cells/hind limb, an increase of 43% compared to WT (p < 0.01), along with the re-emergence of the KSIL population. To determine whether the Hmgb3−/Y lin−, c-kit−, Sca-1+ population contains repopulating HSCs after 4 days of 5-FU treatment similar to WT mice, we performed repopulation assays using KSIL and lin−, c-kit−, Sca-1+ cells sorted from 4 day p.i. 5-FU treated Hmgb3−/Y mice. Recipients received either 2 x 104 KSIL or 2 x 105 lin−, c-kit−, Sca-1+ cells (Ly 5.2) from 5-FU treated Hmgb3−/Y mice along with a radioprotective dose of 3 x 105 congenic (Ly 5.1) bone marrow cells. FACS analysis performed on control recipients transplanted with congenic marrow exhibited < 1% Ly 5.2 cells in the bone marrow 16 weeks after transplant. Pre-5-FU treatment, 88% of bone marrow cells were donor derived in recipients of Hmgb3−/Y KSIL cells. There was no detectable engraftment of Hmgb3−Y lin−, c-kit−, Sca-1+ cells. In contrast to WT mice, both KSIL and lin−, c-kit−, Sca-1+ cells from 5-FU treated Hmgb3−/Y mice were capable of long-term repopulation (62–82% donor derived cells). We conclude that Hmgb3 deficiency facilitates the reemergence of c-kitHI HSCs following 5-FU treatment. Mechanisms involving either enhanced HSC self-renewal or delayed differentiation into CLPs and CMPs are both consistent with our results.

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