Clinical Protocol for a Phase II Study of Leridistim (SC-70935) in Adult Patients (Age>55) With Acute Myeloid Leukemia (AML) Receiving Chemotherapy With the Cytarabine and Daunorubicin "7+3" Regimen

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Colony-stimulating factors such as leridistim and filgrastim increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy.
PURPOSE: Randomized phase II trial to compare the effectiveness of leridistim with that of filgrastim to reduce side effects in older patients who are receiving cytarabine and daunorubicin for acute myeloid leukemia.

Start Date01 Aug 1999

Sponsor / Collaborator

Memorial Sloan Kettering Cancer Center

[+1]

100 Clinical Results associated with CD123 x CSF-3R

100 Translational Medicine associated with CD123 x CSF-3R

0 Patents (Medical) associated with CD123 x CSF-3R

Literatures (Medical) associated with CD123 x CSF-3R

01 Nov 2021·LeukemiaQ1 · MEDICINE

Phenotypic characterization of leukemia-initiating stem cells in chronic myelomonocytic leukemia

Q1 · MEDICINE

Article

Author: Keller, Alexandra ; Slavnitsch, Katharina ; Greiner, Georg ; Gleixner, Karoline V ; Rülicke, Thomas ; Stefanzl, Gabriele ; Sadovnik, Irina ; Bauer, Karin ; Deininger, Michael ; Valent, Peter ; Berger, Daniela ; Bettelheim, Peter ; Sperr, Wolfgang R ; Willmann, Michael ; Sill, Heinz ; Ivanov, Daniel ; Peter, Barbara ; Geissler, Klaus ; Eisenwort, Gregor

Chronic myelomonocytic leukemia (CMML) is a stem cell-derived neoplasm characterized by dysplasia, uncontrolled expansion of monocytes, and substantial risk to transform to secondary acute myeloid leukemia (sAML). So far, little is known about CMML-initiating cells. We found that leukemic stem cells (LSC) in CMML reside in a CD34⁺/CD38^- fraction of the malignant clone. Whereas CD34⁺/CD38^- cells engrafted NSGS mice with overt CMML, no CMML was produced by CD34⁺/CD38⁺ progenitors or the bulk of CD34^- monocytes. CMML LSC invariably expressed CD33, CD117, CD123 and CD133. In a subset of patients, CMML LSC also displayed CD52, IL-1RAP and/or CLL-1. CMML LSC did not express CD25 or CD26. However, in sAML following CMML, the LSC also expressed CD25 and high levels of CD114, CD123 and IL-1RAP. No correlations between LSC phenotypes, CMML-variant, mutation-profiles, or clinical course were identified. Pre-incubation of CMML LSC with gemtuzumab-ozogamicin or venetoclax resulted in decreased growth and impaired engraftment in NSGS mice. Together, CMML LSC are CD34⁺/CD38^- cells that express a distinct profile of surface markers and target-antigens. During progression to sAML, LSC acquire or upregulate certain cytokine receptors, including CD25, CD114 and CD123. Characterization of CMML LSC should facilitate their enrichment and the development of LSC-eradicating therapies.

27 Oct 2020·Blood AdvancesQ2 · MEDICINE

Delineation of target expression profiles in CD34+/CD38− and CD34+/CD38+ stem and progenitor cells in AML and CML

Q2 · MEDICINE

Article

Author: Willmann, Michael ; Bilban, Martin ; Baumgartner, Sigrid ; Sadovnik, Irina ; Herndlhofer, Susanne ; Blatt, Katharina ; Hoermann, Gregor ; Rabitsch, Werner ; Streubel, Berthold ; Schulenburg, Axel ; Sperr, Wolfgang R. ; Greiner, Georg ; Valent, Peter ; Rülicke, Thomas ; Eisenwort, Gregor ; Mueller, Niklas ; Vallera, Daniel A. ; Herrmann, Harald ; Stefanzl, Gabriele

AbstractIn an attempt to identify novel markers and immunological targets in leukemic stem cells (LSCs) in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), we screened bone marrow (BM) samples from patients with AML (n = 274) or CML (n = 97) and controls (n = 288) for expression of cell membrane antigens on CD34+/CD38− and CD34+/CD38+ cells by multicolor flow cytometry. In addition, we established messenger RNA expression profiles in purified sorted CD34+/CD38− and CD34+/CD38+ cells using gene array and quantitative polymerase chain reaction. Aberrantly expressed markers were identified in all cohorts. In CML, CD34+/CD38− LSCs exhibited an almost invariable aberration profile, defined as CD25+/CD26+/CD56+/CD93+/IL-1RAP+. By contrast, in patients with AML, CD34+/CD38− cells variably expressed “aberrant” membrane antigens, including CD25 (48%), CD96 (40%), CD371 (CLL-1; 68%), and IL-1RAP (65%). With the exception of a subgroup of FLT3 internal tandem duplication–mutated patients, AML LSCs did not exhibit CD26. All other surface markers and target antigens detected on AML and/or CML LSCs, including CD33, CD44, CD47, CD52, CD105, CD114, CD117, CD133, CD135, CD184, and roundabout-4, were also found on normal BM stem cells. However, several of these surface targets, including CD25, CD33, and CD123, were expressed at higher levels on CD34+/CD38− LSCs compared with normal BM stem cells. Moreover, antibody-mediated immunological targeting through CD33 or CD52 resulted in LSC depletion in vitro and a substantially reduced LSC engraftment in NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice. Together, we have established surface marker and target expression profiles of AML LSCs and CML LSCs, which should facilitate LSC enrichment, diagnostic LSC phenotyping, and development of LSC-eradicating immunotherapies.

01 Jan 2015·Clinical LaboratoryQ4 · MEDICINE

Expressions of CD96 and CD123 in Bone Marrow Cells of Patients with Myelodysplastic Syndromes

Q4 · MEDICINE

Article

Author: Shao, Zonghong ; Wang, Huaquan ; Fu, Rong ; Liu, Hui ; Zhang, Wei ; Li, Lijuan

BACKGROUNDOur goal was to detect the expression of CD96 and CD123 in myelodysplastic syndromes (MDS) and their proliferation and differentiation characteristics.METHODSForty-three patients with MDS, thirteen AML patients diagnosed in the Hematology Department of General Hospital of Tianjin Medical University, and sixteen healthy controls were enrolled in this study. The expressions of CD96 and CD123 on CD34+CD38- bone marrow cells (BMC) of these patients and controls were measured by FACS. CD114 (GCSFR), EPOR, and CD110 (TPOR) expression on their CD34+CD38-CD96+ and CD34+CD38-CD96- BMC and these cells' apoptosis (Annexin V) were also detected by FACS.RESULTSMDS patients had a significantly higher proportion of CD34+CD38-/CD34+ BMC (22.72 ± 23.91%) than normal controls (8.63 ± 9.35%) (p < 0.01). The expressions of CD34+CD38-CD96+/CD34+CD38- BMC and CD34+ CD38-CD123+/CD34+CD38- BMC of MDS patients (21.18 ± 24.06%, 31.62 ± 28.42%, respectively) were significantly higher than those of normal controls (11.23 ± 17.91%, 9.29 ± 12.63%) (p < 0.01). The expressions of CD34+CD38-CD96+/CD34+CD38- BMC and CD34+CD38-CD123+/CD34+CD38- BMC in the high-risk MDS group (26.25 ± 27.64%, 37.56 ± 31.01%) was significantly higher than those in the low-risk group (11.44 ± 10.88, 15.53 ± 10.96%) (p < 0.05). The expression levels of CD123 and CD96 were significantly correlated with the proportion of bone marrow blasts (r = 0.384, p < 0.05; r = 0.625, p < 0.05). The expressions of CD114, CD110, and Annexin V in CD34+CD38-CD96+ BMC (7.23 ± 10.25%, 0.52 ± 1.23%, 2.96 ± 3.84%, respectively) were significantly lower than those in CD34+CD38-CD96- BMC (24.35 ± 21.74%, 12.03 ± 10.91%, 13.69 ± 17.98%, respectively) of MDS patients (p < 0.05).CONCLUSIONSThere was a higher proportion of CD34+CD38-CD96+ and CD34+CD38-CD123+ cells in bone marrow of MDS patients. Those cells expressed lower cytokine receptors and displayed lower apoptosis. Leukemia stem cells (LSC) in MDS might be contained in those cells.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis