The Evidence of Clonal Evolution with Monosomy 7 in Aplastic Anemia Following Granulocyte Colony-Stimulating Factor Using the Polymerase Chain Reaction

1997 ◽  
Vol 23 (2) ◽  
pp. 213-218 ◽  
Author(s):  
Etsuko Yamazaki ◽  
Heiwa Kanamori ◽  
Jun Taguchi ◽  
Hiroshi Harano ◽  
Hiroshi Mohri ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Aplastic Anemia ◽  
Clonal Evolution ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Chain Reaction ◽  
Monosomy 7 ◽  
Polymerase Chain ◽  
Stimulating Factor

scholarly journals Human FLT3/FLK2 gene: cDNA cloning and expression in hematopoietic cells

Blood ◽  
1993 ◽  
Vol 82 (4) ◽  
pp. 1110-1119 ◽  
Author(s):  
O Rosnet ◽  
C Schiff ◽  
MJ Pebusque ◽  
S Marchetto ◽  
C Tonnelle ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Tyrosine Kinase ◽  
B Cell ◽  
Cloning And Expression ◽  
Colony Stimulating Factor ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
Stimulating Factor

The human FLT3 cDNA was cloned from a pre-B cell line and characterized. The deduced amino acid sequence shows that FLT3 codes for a receptor-type tyrosine kinase of 993 residues, presenting a strong similarity with the corresponding mouse FLT3/FLK2 protein as well as with the receptors for colony-stimulating factor 1 (CSF1R/FMS) and steel locus factor (SLFR/KIT). An analysis of the expression of the gene using amplification of reverse transcribed FLT3 mRNA by polymerase chain reaction shows that FLT3 is expressed in various lymphohematopoietic cells and tissues, including a series of immature cell lines and leukemias of lymphocytic origin.

Antilymphocyte globulin, cyclosporine, prednisolone, and granulocyte colony-stimulating factor for severe aplastic anemia: an update of the GITMO/EBMT study on 100 patients

Blood ◽  
2000 ◽  
Vol 95 (6) ◽  
pp. 1931-1934 ◽  
Author(s):  
A. Bacigalupo ◽  
B. Bruno ◽  
P. Saracco ◽  
E. Di Bona ◽  
A. Locasciulli ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Clonal Evolution ◽  
Severe Aplastic Anemia ◽  
Granulocyte Colony Stimulating Factor ◽  
Antilymphocyte Globulin ◽  
Colony Stimulating Factor ◽  
Actuarial Survival ◽  
First Line Therapy ◽  
Stimulating Factor ◽  
Median Interval

Abstract One hundred consecutive patients with severe aplastic anemia (SAA) received horse antilymphocyte globulin (ALG), cyclosporin A (CyA), 6-methylprednisolone (6Mpred), and granulocyte colony-stimulating factor (G-CSF) as first-line therapy. The median age was 16 years (range, 1-72 years) and median neutrophil count was 0.2 × 109/L (range, 0-0.5 × 109/L). Trilineage hematologic recovery (at a median interval of 96 days from treatment) was seen in 77 patients (48 complete, 29 partial) after 1 (n = 50) or more courses of ALG (n = 27). Of the 23 nonresponders, 11 patients died at a median interval of 83 days (range, 16-1132 days), 6 were considered treatment failures and underwent transplantation, and 6 were pancytopenic. Cytogenetic abnormalities were seen in 11% of patients, clonal hematologic disease in 8%, and relapse of marrow aplasia in 9%. The actuarial survival at 5 years was 87% (median follow-up 1424 days): 76% versus 98% for patients with neutrophil counts less than versus greater than 0.2 × 109/L (P = .001) and 88% versus 87% for patients aged less than versus more than 16 years (P = .8). The actuarial probability of discontinuing CyA was 38%. Patients who did not achieve a white blood cell (WBC) count of 5 × 109/L during G-CSF treatment have a low probability of responding (37%) and a high mortality rate (42%). This update confirms a high probability for SAA patients of becoming transfusion independent and of surviving after treatment with ALG, CyA, 6Mpred, and G-CSF, with a significant effect of neutrophil counts on outcome. Problems still remain, such as absent or incomplete responses, clonal evolution, relapse of the original disease, and cyclosporine dependence. Early transplantation, also from alternative donors, may be warranted in patients with poor WBC response to G-CSF.

Granulocyte Colony Stimulating Factor Preferentially Causes Proliferation of Pre-Existing Monosomy 7 Cells in Aplastic Anemia and Myelodysplastic Syndrome Because of Abnormal Truncated GCSF-Receptors on These Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 458-458 ◽  
Author(s):  
Elaine M. Sloand ◽  
Shakti Ramkissoon ◽  
Lori Mainwaring ◽  
John Barrett ◽  
Neal S. Young
Keyword(s):  
Signal Transduction ◽  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Aplastic Anemia ◽  
Mononuclear Cells ◽  
Prolonged Exposure ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Monosomy 7 ◽  
Stimulating Factor

Abstract Administration of granulocyte colony stimulating factor (GCSF) has been linked to development of monosomy 7 in some patients with aplastic anemia (AA) and congenital neutropenia. We assessed the effect of GCSF on monosomy 7 to determine if this chromosomal abnormality developed de novo or if GCSF simply favored expansion of a pre-existing clone. Bone marrow mononuclear cells (BMMNC) were co-cultured for 14 days with pharmacological doses of GCSF and examined by fluorescent in situ hybridization (FISH). No karyotypically healthy control, AA, or myelodysplastic syndrome (MDS) bone marrow showed development of monosomy 7. In BMMNC cultures from thirteen patients with MDS and monosomy 7, all developed substantial increases in numbers of monosomy 7 cells after prolonged exposure to GCSF. Experiments on stored AA samples obtained six months prior to the development of abnormal karyotype showed monosomy 7 on FISH ,with expansion of that clone on co-culture with GCSF. GCSFR mRNA was increased in BM from monosomy 7 patients as measured by real time PCR, and monosomy 7 cells expressed more GCSFR on the cell surface than did normal cells. As a truncated GCSFR isoform is associated with a hyperproliferative response to G-CSF and prolonged activation of signal transducer and activator of transcription (STAT) complexes, we sequenced the GCSFR DNA of monosomy 7 cells and measured the expression of the truncated GCSFR mRNA relative to full length GCSFR in patients with monosomy 7. While genomic GCSFR DNA showed no abnormalities, mRNA demonstrated increased proportions of the truncated isoform IV in all six patients tested. We examined GCSF-mediated GCSFR signal transduction of the Jak/Stat system in monosomy 7 CD34 cells. STAT-1 was increased and the STAT 5: STAT 3 rato was increased by ten-fold in all patients with monosomy 7 compared to normals and to MDS with normal cytogenetics. In conclusion, pharmacologic doses of GCSF appear to increase the proportion of monosomy 7 cells; this heightened sensitivity to GCSFmay be related to altered amounts of the truncated form of the receptor, with changes in GCSF signal transduction resulting in expansion of the monosomy 7 clone.

The Risk of Clonal Evolution of Granulocyte Colony-Stimulating Factor for Acquired Aplastic Anemia: A Systematic Review and Meta-Analysis

2018 ◽  
Vol 140 (3) ◽  
pp. 141-145
Author(s):  
Shao-xue Ding ◽  
Tong Chen ◽  
Ting Wang ◽  
Chun-yan Liu ◽  
Wen-li Lu ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Clonal Evolution ◽  
Meta Analysis ◽  
Malignant Neoplasm ◽  
Significant Heterogeneity ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Secondary Malignant Neoplasm ◽  
To Receive ◽  
Stimulating Factor

Objectives: This meta-analysis aimed to evaluate the risk of clonal evolution of granulocyte colony-stimulating factor (G-CSF) in acquired aplastic anemia (AA), and whether the use of G-CSF increases the occurrence of secondary malignant neoplasms, mainly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) or paroxysmal nocturnal hemoglobinuria (PNH). Methods: Data were gathered from randomized controlled trials (RCTs) to evaluate the effect of G-CSF versus no G-CSF at the risk of developing the clonal complications of acquired AA. Electronic searches in PubMed, Embase, and the Cochrane Library were performed to identify studies up to 1 January 2017. Only RCTs performed on patients who were randomly assigned to receive G-CSF or not to receive G-CSF were included. Results: Four relevant trials that met the inclusion criteria were identified. In a pooled analysis, the G-CSF groups of AA patients were not associated with a statistically significant higher occurrence of secondary malignant neoplasm, mainly MDS and AML (relative risk [RR] 0.86; 95% confidence interval [CI] 0.34–2.19; 4 trials). No significant heterogeneity was found (p = 0.67, I2 = 0%). There was no statistically significant higher occurrence of PNH in the G-CSF groups with AA (RR 1.17; 95% CI 0.51–2.71; 4 trials) and no significant heterogeneity was found (p = 0.42, I2 = 0%). Conclusions: G-CSF for patients with AA is not associated with a higher occurrence of secondary malignant neoplasm, mainly MDS/AML, or PNH.

scholarly journals Human FLT3/FLK2 gene: cDNA cloning and expression in hematopoietic cells

Blood ◽  
1993 ◽  
Vol 82 (4) ◽  
pp. 1110-1119 ◽  
Author(s):  
O Rosnet ◽  
C Schiff ◽  
MJ Pebusque ◽  
S Marchetto ◽  
C Tonnelle ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Tyrosine Kinase ◽  
B Cell ◽  
Cloning And Expression ◽  
Colony Stimulating Factor ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
Stimulating Factor

Abstract The human FLT3 cDNA was cloned from a pre-B cell line and characterized. The deduced amino acid sequence shows that FLT3 codes for a receptor-type tyrosine kinase of 993 residues, presenting a strong similarity with the corresponding mouse FLT3/FLK2 protein as well as with the receptors for colony-stimulating factor 1 (CSF1R/FMS) and steel locus factor (SLFR/KIT). An analysis of the expression of the gene using amplification of reverse transcribed FLT3 mRNA by polymerase chain reaction shows that FLT3 is expressed in various lymphohematopoietic cells and tissues, including a series of immature cell lines and leukemias of lymphocytic origin.

Trilineage Response in Severe Aplastic Anemia Following Long-Term Therapy with Recombinant Human Granulocyte Colony-Stimulating Factor

1993 ◽  
Vol 90 (3) ◽  
pp. 159-161 ◽  
Author(s):  
Eishi Ashihara ◽  
Chihiro Shimazaki ◽  
Toshiyuki Hirata ◽  
Katsunori Okawa ◽  
Naritoshi Oku ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Severe Aplastic Anemia ◽  
Term Therapy ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Long Term Therapy ◽  
Stimulating Factor

Methimazole-Induced Aplastic Anemia in Third Exposure: Successful Treatment with Recombinant Human Granulocyte Colony-Stimulating Factor

Thyroid ◽  
1998 ◽  
Vol 8 (9) ◽  
pp. 791-794 ◽  
Author(s):  
P. MEZQUITA ◽  
V. LUNA ◽  
M. MUÑOZ-TORRES ◽  
E. TORRES-VELA ◽  
F. LOPEZ-RODRIGUEZ ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Successful Treatment ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor
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