Study of Bone Marrow Samples From Patients With Acute Leukemia

Identifying the Genetic Basis of Adult AMKL

RATIONALE: Studying the genes expressed in samples of bone marrow from patients with cancer may help doctors identify biomarkers related to cancer.

PURPOSE: This research study is looking at bone marrow samples from patients with acute leukemia.

Study Overview

• Status: Completed
• Conditions: Leukemia
• Intervention / Treatment: Genetic: gene expression analysis; Genetic: polymorphism analysis; Other: laboratory biomarker analysis; Genetic: mutation analysis; Other: flow cytometry; Genetic: protein analysis

Detailed Description

OBJECTIVES:

• To perform high throughput sequencing of a set of megakaryocyte specific transcription factors, tyrosine kinases, and Src kinases in DNA isolated from bone marrow specimens of adults with acute megakaryoblastic leukemia (AMKL).
• To assay the ability of Src kinase inhibitors (SU6656, dasatinib) to induce differentiation of AMKL blasts in these patients.

OUTLINE: DNA from previously collected bone marrow samples are sequenced to analyze genes associated with transcription factors (GATA1, GATA2, SCL, FOG-1, ETS1, ETS2, ERG, FLI-1, GABP, HOXA11, NF-E2, and RUNX1), tyrosine kinases (JAK2, JAK3, and c-MPL), and Src family kinases (LYN, FYN, and HCK) and compared with control DNA. Using bioinformatics, gene alterations are compared to known polymorphisms and subsequent changes in the amino acid sequence of the encoded protein. Subsequent assays assess the effect on proliferation and differentiation and in vitro studies evaluate the consequences of mutations on transcription factor and kinase activity abilities. The effect of SU6656 and dasatinib on cell death and polyploidization is evaluated by flow cytometry and compared with control DNA.

• Study Type: Observational
• Enrollment (Actual): 40

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with Acute Leukemia

Description

DISEASE CHARACTERISTICS:

• Diagnosis of adult acute megakaryoblastic leukemia
• Archived bone marrow specimens from the ECOG tissue repository

PATIENT CHARACTERISTICS:

• Not specified

PRIOR CONCURRENT THERAPY:

• Not specified

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Correlation of gene mutations with adult acute megakaryoblastic leukemia (AMKL)	1 year

Collaborators and Investigators

• Sponsor: Eastern Cooperative Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: John Crispino, PhD, Robert H. Lurie Cancer Center

Study record dates

Study Major Dates

• Study Start: July 3, 2008
• Primary Completion (ACTUAL): November 11, 2009
• Study Completion (ACTUAL): November 11, 2009

Study Registration Dates

• First Submitted: May 9, 2009
• First Submitted That Met QC Criteria: May 9, 2009
• First Posted (ESTIMATE): May 12, 2009

Study Record Updates

• Last Update Posted (ACTUAL): May 17, 2017
• Last Update Submitted That Met QC Criteria: May 16, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: adult acute megakaryoblastic leukemia (M7)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia
• Other Study ID Numbers: CDR0000600323; ECOG-E1900T3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data sharing is dictated by the group's data sharing plan.