scholarly journals A diverged homeobox gene is involved in the proliferation and lineage commitment of human hematopoietic progenitors and highly expressed in acute myelogenous leukemia

Blood ◽  
1992 ◽  
Vol 79 (11) ◽  
pp. 2841-2848 ◽  
Author(s):  
Y Deguchi ◽  
A Kirschenbaum ◽  
JH Kehrl
Keyword(s):  
Bone Marrow ◽  
Acute Myelogenous Leukemia ◽  
Homeobox Gene ◽  
Cell Types ◽  
Myelogenous Leukemia ◽  
Specific Cell ◽  
Hematopoietic Progenitors ◽  
Hematopoietic Progenitor ◽  
Cd34 Cells ◽  
Acute Myelogenous

Abstract HB24 is a diverged homeobox gene known to be expressed in hematopoietic progenitor cells. We show here that the inhibition of HB24 expression in CD34+ bone marrow cells via antisense (AS) oligonucleotides impaired the proliferation of these cells in response to interleukin-3 and granulocyte-macrophage colony-stimulating factor. The treatment of CD34+ cells with HB24 AS oligonucleotides also reduced the levels of c- fos, c-myc, c-myb, cyclin B, and p34cdc2 messenger RNAs compared with cells treated with control oligonucleotides. Conversely, the transient transfection of HB24 into a subpopulation of CD34 cells inhibited their differentiation into mature hematopoietic cell types. In addition, HB24 messenger RNA transcripts were elevated in bone marrow and peripheral blood mononuclear cells isolated from patients with acute myelogenous leukemia compared with normal controls. These data suggest that HB24 is an important transcription factor during hematopoietic progenitor proliferation and that differentiation to specific cell types requires its downregulation. Furthermore, dysregulated expression of HB24 impairs the normal differentiation of hematopoietic progenitors and may contribute to leukemogenesis.

scholarly journals A diverged homeobox gene is involved in the proliferation and lineage commitment of human hematopoietic progenitors and highly expressed in acute myelogenous leukemia

Blood ◽  
1992 ◽  
Vol 79 (11) ◽  
pp. 2841-2848 ◽  
Author(s):  
Y Deguchi ◽  
A Kirschenbaum ◽  
JH Kehrl
Keyword(s):  
Bone Marrow ◽  
Acute Myelogenous Leukemia ◽  
Homeobox Gene ◽  
Cell Types ◽  
Myelogenous Leukemia ◽  
Specific Cell ◽  
Hematopoietic Progenitors ◽  
Hematopoietic Progenitor ◽  
Cd34 Cells ◽  
Acute Myelogenous

HB24 is a diverged homeobox gene known to be expressed in hematopoietic progenitor cells. We show here that the inhibition of HB24 expression in CD34+ bone marrow cells via antisense (AS) oligonucleotides impaired the proliferation of these cells in response to interleukin-3 and granulocyte-macrophage colony-stimulating factor. The treatment of CD34+ cells with HB24 AS oligonucleotides also reduced the levels of c- fos, c-myc, c-myb, cyclin B, and p34cdc2 messenger RNAs compared with cells treated with control oligonucleotides. Conversely, the transient transfection of HB24 into a subpopulation of CD34 cells inhibited their differentiation into mature hematopoietic cell types. In addition, HB24 messenger RNA transcripts were elevated in bone marrow and peripheral blood mononuclear cells isolated from patients with acute myelogenous leukemia compared with normal controls. These data suggest that HB24 is an important transcription factor during hematopoietic progenitor proliferation and that differentiation to specific cell types requires its downregulation. Furthermore, dysregulated expression of HB24 impairs the normal differentiation of hematopoietic progenitors and may contribute to leukemogenesis.

Transcription of AML1/ETO in bone marrow and cord blood of individuals without acute myelogenous leukemia

Blood ◽  
2002 ◽  
Vol 100 (6) ◽  
pp. 2267-2267 ◽  
Author(s):  
Jorg Basecke ◽  
Lukas Cepek ◽  
Christine Mannhalter ◽  
Jurgen Krauter ◽  
Stefanie Hildenhagen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cord Blood ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Acute Myelogenous

Loss of the Y Chromosome: An Age-Related or Clonal Phenomenon in Acute Myelogenous Leukemia/Myelodysplastic Syndrome?

2008 ◽  
Vol 132 (8) ◽  
pp. 1329-1332
Author(s):  
Anna K. Wong ◽  
Belle Fang ◽  
Ling Zhang ◽  
Xiuqing Guo ◽  
Stephen Lee ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Y Chromosome ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Related Phenomenon ◽  
Patients Âgés ◽  
Age Related ◽  
Acute Myelogenous ◽  
Bone Marrow Analysis

Abstract Context.—The clinical association between loss of the Y chromosome and acute myelogenous leukemia and myelodysplastic syndrome (AML/MDS) has been debated because both phenomena are related to aging. A prior publication suggests that loss of the Y chromosome in more than 75% of cells may indicate a clonal phenomenon that could be a marker for hematologic disease. Objective.—To evaluate the relationship between loss of the Y chromosome and AML/MDS. Design.—A retrospective review of cytogenetic reports of 2896 male patients ascertained from 1996 to 2007 was performed. Results were stratified based on the percentage of cells missing the Y chromosome and were correlated with patients' ages and bone marrow biopsy reports through logistic regression analysis with adjustment for age. Results.—Loss of the Y chromosome was found in 142 patients. Of these, 16 patients demonstrated myeloid disease, with 2 cases of AML and 14 cases of MDS. An increased incidence (P < .05) of AML/MDS was seen only in the group composed of 8 patients with complete loss of the Y chromosome in all karyotyped cells (1 case of AML and 7 cases of MDS). Conclusion.—Loss of the Y chromosome appears to be primarily an age-related phenomenon. However, in individuals in which all cells on cytogenetic analysis showed loss of the Y chromosome, there was a statistically significant increase in AML/MDS, suggesting that the absence of any normal-dividing cells in a bone marrow analysis may be indicative of AML/MDS.

Prospective comparative study of bone marrow transplantation and postremission chemotherapy for childhood acute myelogenous leukemia. The Associazione Italiana Ematologia ed Oncologia Pediatrica Cooperative Group.

1993 ◽  
Vol 11 (6) ◽  
pp. 1046-1054 ◽  
Author(s):  
S Amadori ◽  
A M Testi ◽  
M Aricò ◽  
A Comelli ◽  
M Giuliano ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Acute Myelogenous Leukemia ◽  
Marrow Transplantation ◽  
Autologous Bone Marrow Transplantation ◽  
Myelogenous Leukemia ◽  
Allogeneic Bone ◽  
Free Survival ◽  
Acute Myelogenous ◽  
First Remission

PURPOSE This study was conducted to assess the comparative values of allogeneic bone marrow transplantation (BMT) and autologous bone marrow transplantation (ABMT) with sequential postremission chemotherapy (SPC) in children with acute myelogenous leukemia (AML) in first remission. PATIENTS AND METHODS From March 1987 to March 1990, 161 assessable patients younger than 15 years of age with newly diagnosed AML were treated uniformly with two courses of daunorubicin and standard-dose cytarabine. After initial consolidation with a course of daunorubicin, cytarabine, and thioguanine (DAT), patients in complete remission (CR) were randomized to receive either ABMT or SPC, except for those with an HLA-matched sibling who were assigned to undergo BMT. SPC consisted of three additional courses of DAT, followed by three pairs of drugs administered sequentially for a total of six cycles. RESULTS Overall, 127 of 161 patients attained CR (79%). The estimated probabilities of survival and event-free survival (EFS) at 5 years for all patients were 42% and 25%, respectively (median follow-up, 28 months). For the 127 complete responders, the 5-year probability of disease-free survival (DFS) was 31%, with a cumulative risk of relapse of 64%. For the purpose of this study, all complete responders were evaluated for analysis of disease outcome according to the intent-to-treat principle, regardless of whether they actually received the intended therapy. The 5-year DFS was 51% for the BMT group (n = 24), significantly higher (P = .03) than that observed for the other cohorts: 21% for ABMT (n = 35), 27% for SPC (n = 37), and 34% for a group of 31 nonrandomized (NR) patients. Bone marrow relapse was the most frequent cause of postremission failure in all therapeutic subgroups, including the BMT cohort, in which no deaths attributable to the toxicity of the procedure were recorded. CONCLUSION The results of this study show that BMT is more effective than ABMT or SPC in preventing leukemia relapse and extending DFS duration in children with AML in first remission.

Does cranial irradiation reduce the risk for bone marrow relapse in acute myelogenous leukemia? Unexpected results of the Childhood Acute Myelogenous Leukemia Study BFM-87.

1993 ◽  
Vol 11 (2) ◽  
pp. 279-286 ◽  
Author(s):  
U Creutzig ◽  
J Ritter ◽  
M Zimmermann ◽  
G Schellong
Keyword(s):  
Bone Marrow ◽  
Acute Myelogenous Leukemia ◽  
Cranial Irradiation ◽  
Low Risk ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Number Of Patients ◽  
Acute Myelogenous ◽  
Wbc Count ◽  
Group B

PURPOSE One of the goals of study AMA-BFM-87 was to test prospectively in acute myelogenous leukemia (AML) patients if cranial irradiation could be replaced by late intensification therapy with high-dose cytarabine (Ara-C) and etoposide (VP-16). PATIENTS AND METHODS Patients with a low risk of CNS relapses (ie, no initial CNS disease, WBC count at diagnosis < or = 70.000/microL) were randomized for irradiation (group A, 31 patients). In 25 patients (group B), randomization was refused. As interim results showed no increase of CNS relapses in nonirradiated patients, prophylactic irradiation was discontinued after 2 1/2 years to prevent unnecessary CNS toxicity. Forty-four patients (group C) entered the study after randomization had been stopped. RESULTS In all patients with a low risk of CNS recurrences (n = 100), a significantly higher probability of relapse-free interval (pRFI) of 5 years was found in irradiated patients (pRFI = .78) compared with nonirradiated patients (pRFI = .41) (P = .007). Moreover, a slightly higher incidence of CNS relapses was observed in nonirradiated patients. Due to the small number of patients, this was not observed when randomized patients only were analyzed. In accordance with these findings, the favorable outcome of low-risk patients in the preceding study, AML-BFM-83 (pRFI > .80), could only be reproduced in study AML-BFM-87 in patients who had received cranial irradiation. CONCLUSION These results indicate that cranial irradiation should be an integral part of the treatment of all AML patients not undergoing bone marrow transplantation. Residual blasts in the CNS may escape systemic chemotherapy and lead to recurrence of the initial disease not only in the CNS, but also in the bone marrow.

scholarly journals Gene Rearrangements in Bone Marrow Cells of Patients with Acute Myelogenous Leukemia

2000 ◽  
Vol 103 (3) ◽  
pp. 125-134 ◽  
Author(s):  
H.M. Schmetzer ◽  
S. Braun ◽  
D. Wiesner ◽  
T. Duell ◽  
H.H. Gerhartz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myelogenous Leukemia ◽  
Bone Marrow Cells ◽  
Myelogenous Leukemia ◽  
Gene Rearrangements ◽  
Acute Myelogenous ◽  
Marrow Cells

Therapy-Related Myelodysplasia and Secondary Acute Myelogenous Leukemia After High-Dose Therapy With Autologous Hematopoietic Progenitor-Cell Support for Lymphoid Malignancies

2000 ◽  
Vol 18 (5) ◽  
pp. 947-947 ◽  
Author(s):  
Ivana N. M. Micallef ◽  
Debra M. Lillington ◽  
John Apostolidis ◽  
John A. L. Amess ◽  
Michael Neat ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cell ◽  
Myelogenous Leukemia ◽  
Hematopoietic Progenitor Cell ◽  
High Dose ◽  
High Dose Therapy ◽  
Hematopoietic Progenitor ◽  
Acute Myelogenous ◽  
Cell Support

PURPOSE: To evaluate the incidence of and risk factors for therapy-related myelodysplasia (tMDS) and secondary acute myelogenous leukemia (sAML), after high-dose therapy (HDT) with autologous bone marrow or peripheral-blood progenitor-cell support, in patients with non-Hodgkin’s lymphoma (NHL). PATIENTS AND METHODS: Between January 1985 and November 1996, 230 patients underwent HDT comprising cyclophosphamide therapy and total-body irradiation, with autologous hematopoietic progenitor-cell support, as consolidation of remission. With a median follow-up of 6 years, 27 (12%) developed tMDS or sAML. RESULTS: Median time to development of tMDS or sAML was 4.4 years (range, 11 months to 8.8 years) after HDT. Karyotyping (performed in 24 cases) at diagnosis of tMDS or sAML revealed complex karyotypes in 18 patients. Seventeen patients had monosomy 5/5q−, 15 had −7/7q−, seven had −18/18q−, seven had −13/13q−, and four had −20/20q−. Twenty-one patients died from complications of tMDS or sAML or treatment for tMDS or sAML, at a median of 10 months (range, 0 to 26 months). Sixteen died without evidence of recurrent lymphoma. Six patients were alive at a median follow-up of 6 months (range, 2 to 22 months) after diagnosis of tMDS or sAML. On multivariate analysis, prior fludarabine therapy (P = .009) and older age (P = .02) were associated with the development of tMDS or sAML. Increased interval from diagnosis to HDT and bone marrow involvement at diagnosis were of borderline significance (P = .05 and .07, respectively). CONCLUSION: tMDS and sAML are serious complications of HDT for NHL and are associated with very poor prognosis. Alternative strategies for reducing their incidence and for treatment are needed.

Sign in / Sign up

Export Citation Format

Share Document