Lineage-unrestricted hematologic response to granulocyte colony-stimulating factor in a patient with refractory anemia with excess blasts

Yokose, Norio; Ogata, Kíyoyuki; An, Emi; Tamura, Hideto; Kamikubo, K; Dan, Kazuo; Nomura, Takeo

doi:10.1007/bf01682038

Cited by 4 publications

(3 citation statements)

References 17 publications

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“…Histologic sections of the bone marrow, which were prepared from the aspirated bone marrow and stained with haematoxylin–eosin, were available for 14 RA cases, seven RAEB and 10 RAEB‐t cases. The method for preparing the histologic sections, from which contamination by peripheral blood was well‐eliminated, and examples of the histologic sections were reported previously ( Yokose et al , 1995 ; Tamura et al , 1997 ). These sections were examined with a microscope connected to a Micro‐Videomat 2 (Zeiss, Oberkochen, Germany), using a relatively high‐power field (×400) to identify micromegakaryocytes as well as normal‐sized megakaryocytes.…”

Section: Methodsmentioning

confidence: 99%

Plasma thrombopoietin (TPO) levels and expression of TPO receptor on platelets in patients with myelodysplastic syndromes

Tamura¹,

Ogata²,

Luo³

et al. 1998

Br J Haematol

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Summary. Data on endogenous thrombopoietin (TPO) levels and their regulation in myelodysplastic syndromes (MDS) are sparse. We examined the plasma TPO level of 85 MDS patients by a sensitive enzyme immunoassay and the platelet expression of TPO receptor (TPO-R) protein, which metabolizes endogenous TPO, in 19 MDS patients with an equilibrium binding assay using 125 I-TPO. The MDS patients had higher plasma TPO levels (7·0 Ϯ 9·3 fmol/ml) than 52 normal subjects (P < 0·0001). Refractory anaemia (RA) patients (n ¼ 39) had higher plasma TPO levels than patients (n ¼ 28) with RA with excess blasts (RAEB) or RAEB in transformation (RAEB-t) (P ¼ 0·0002), irrespective of similar platelet counts in these groups. The plasma TPO level correlated inversely with the platelet count in RA patients (P ¼ 0·0027) but not in RAEB and RAEB-t patients (P ¼ 0·7865). These data suggest that the physiological pathway for TPO production and metabolism is conserved, at least partially, in RA, but deranged in RAEB/RAEB-t. The number of TPO-R per platelet was significantly smaller in 19 MDS patients (17·5 Ϯ 13·3) than in normals (P ¼ 0·0014), but similar between RA patients and patients with RAEB and RAEB-t. Further, the bone marrow megakaryocyte count, determined in 31 MDS patients, was quite similar between RA patients and patients with RAEB or RAEB-t. Thus, in addition to thrombocytopenia, a reduced platelet TPO-R number may contribute to elevated plasma TPO levels in MDS, and a regulatory pathway for circulating TPO other than platelet TPO-R and marrow megakaryocytes, such as blasts expressing TPO-R, may operate in RAEB/RAEB-t.

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Section: Methodsmentioning

confidence: 99%

Plasma thrombopoietin (TPO) levels and expression of TPO receptor on platelets in patients with myelodysplastic syndromes

Tamura¹,

Ogata²,

Luo³

et al. 1998

Br J Haematol

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“…Recently, it has been reported that hematological disorders in some patients with MDS improved following treatment with G-CSF (Nagler et al, 1995;Yokose et al, 1995). However, this mechanism has not yet been clari®ed.…”

Section: Discussionmentioning

confidence: 96%

“…Some cases with MDS show a quantitative hematological recovery of one or more cell lineages responding to G-CSF treatment (Nagler et al, 1995;Yokose et al, 1995). This mechanism has not yet been clarified.…”

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confidence: 96%

New human myelodysplastic cell line, TER‐3: G‐CSF specific downregulation of Ca²⁺/calmodulin‐dependent protein kinase IV

Mishima

Terui

Mishima

et al. 2002

Journal Cellular Physiology

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We have established a new hematopoietic cell line from a patient with myelodysplastic syndrome (MDS), which was refractory anemia with excess blasts (RAEB). This cell line, designated TER-3, depends on several cytokines for long-term survival and growth, and requires interleukin-3 (IL-3) for continuous growth. Cytochemical analysis revealed that TER-3 cells are weakly dianisidine positive and nonspecific esterase positive, but peroxidase negative. The surface marker profile shows that the TER-3 cells are strongly positive for myeloid, lymphoid, and megakaryocytic antigens such as CD15, CD19, and CD61, and negative for some common multilineage antigens such as CD13, CD33, and CD34. Thus, this cell line has a multilineage phenotype, suggesting that the transformation event occurred in multipotent stem cells. Dianisidine- and nonspecific esterase-positive TER-3 cells increase with granulocyte-colony stimulating factor (G-CSF) rather than with IL-3. These results suggest that the cell line is useful for understanding the mechanism underlying G-CSF-associated hematopoietic cell differentiation and activation in the patient with MDS.

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Myelodysplastic Syndromes

2007

Veterinary Comparative Hematopathology

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SynopsisThe myelodysplastic syndromes are a diverse group of clonal stem cell disorders characterized by ineffective hematopoiesis, peripheral cytopenias, and an increased propensity to evolve to acute myeloid leukemia. The molecular pathogenesis of these disorders is poorly understood, but recurring chromosomal abnormalities occur in ~50% of cases, and are the focus of much investigation. The availability of newer molecular techniques has allowed the identification of additional genetic aberrations, including mutations and epigenetic changes of prognostic and potential therapeutic importance. This review will focus on the key role of cytogenetic analysis in MDS in the context of the diagnosis, prognosis, and pathogenesis of these disorders.Keywords myelodysplastic syndromes; cytogenetics; molecular genetics; diagnosis; prognosis; classification IntroductionThe myelodysplastic syndromes (MDS) include a large spectrum of clonal hematopoietic stem cell disorders that are characterized by peripheral cytopenia(s), morphologic dysplasia, ineffective hematopoiesis, and a variable propensity to transform to acute myeloid leukemia (AML). 1,2 The cytopenia can be limited to a single cell line resulting in anemia, This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript thrombocytopenia, or neutropenia, and can be chronic and somewhat indolent, or profound involving all three lineages with life-threatening consequences. The morphologic dysplasia associated with the ineffective hematopoiesis may be subtle and difficult to recognize but, in some cases, it can be impressive and evident in both the bone marrow and peripheral blood. The variable increase in blasts relates, in part, to the risk for transformation to AML, although progression is not solely dependent on the blast percentage. MDS is a disease of older adults with a median age at diagnosis of ~70 years 3 . Other risk factors for the development of MDS include tobacco use and exposure to solvents, such as benzene and agricultural chemicals. In ~10-15% of cases, the disease arises as a late complication of cytotoxic therapy (radiotherapy and/or chemotherapy) for a prior disorder, and is referred to as a therapy-related myeloid neoplasm (t-MN). MDS is frequently associated with clonal cytogenetic abnormalities, of significant prognostic 4,5 and emerging therapeutic importance. An in-depth analysis of some of these is providing significant insights into underlying molecular alterations, which may hold clues to unraveling the pathogenesis of these disorders. This review will focus on the ...

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Lineage-unrestricted hematologic response to granulocyte colony-stimulating factor in a patient with refractory anemia with excess blasts

Cited by 4 publications

References 17 publications

Plasma thrombopoietin (TPO) levels and expression of TPO receptor on platelets in patients with myelodysplastic syndromes

Plasma thrombopoietin (TPO) levels and expression of TPO receptor on platelets in patients with myelodysplastic syndromes

New human myelodysplastic cell line, TER‐3: G‐CSF specific downregulation of Ca²⁺/calmodulin‐dependent protein kinase IV

Myelodysplastic Syndromes

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Lineage-unrestricted hematologic response to granulocyte colony-stimulating factor in a patient with refractory anemia with excess blasts

Cited by 4 publications

References 17 publications

Plasma thrombopoietin (TPO) levels and expression of TPO receptor on platelets in patients with myelodysplastic syndromes

Plasma thrombopoietin (TPO) levels and expression of TPO receptor on platelets in patients with myelodysplastic syndromes

New human myelodysplastic cell line, TER‐3: G‐CSF specific downregulation of Ca2+/calmodulin‐dependent protein kinase IV

Myelodysplastic Syndromes

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Product

Resources

About

New human myelodysplastic cell line, TER‐3: G‐CSF specific downregulation of Ca²⁺/calmodulin‐dependent protein kinase IV