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Myeloid Leukemia

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Imatinib Mesylate

bone marrow aspiration

Jeff Lipton, MD

Martin Blackstein, MD

In order to distinguish between clonal instability driven by imatinib in CML and actual changes with secondary clones induced by imatinib we would like to investigate the karyotype of non-CML patients treated with imatinib such as GIST patients.

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the presence of the Philadelphia (Ph) chromosome - a t(9:22) translocation that results in the production of a BCR/ABL fusion protein with Abl kinase activity.

Imatinib mesylate (Gleevec) specifically targets a limited set of protein tyrosine kinases - ABL, Arg (Abl-related gene), c-Kit, platelet-derived growth factor receptor (PDGF-R) - and their oncogenic forms, most notably BCR/ABL Imatinib is also a potent inhibitor of a receptor-type c-Kit tyrosine kinase. Therefore imatinib was examined for therapeutic efficacy against malignant gastro-intestinal stromal tumors (GIST) Recent articles have drawn attention to the development of new Ph-negative, cytogenetically unrelated clones after therapy of Ph-positive CML with imatinib. Trisomy 8 and monosomy 7 are the most frequent defects, but other aberrations have also been reported. Some of these cytogenetic abnormalities are associated with acute myeloid leukemia and MDS.

Chromosome Abnormalities in Chronic Myeloid Leukemia (CML) on Imatinib. GIST Patients on Imatinib

Are the Secondary Chromosome Abnormalities Seen in Chronic Myeloid Leukemia (CML) Cells Induced to Ph-Chromosome Negativity by Imatinib a Result of Chromosome Instability or a Side Effect of the Therapy - a Study in GIST (Gastrointestinal Stromal Cell Tumors) Patients Treated With Imatinib.

Princess Margaret Hospital, Canada

Mount Sinai Hospital, Canada

Novartis

University Health Network, Toronto

Dr. Jeff Lipton

Specific Aim 1: To determine patient compliance with a GIST surveillance program Hypothesis: Patient compliance with a GIST surveillance program will be low.

Specific Aim 2: To determine if EUS features of GIST, particularly maximum size, change significantly during a surveillance program.

Hypothesis: EUS features of GIST, particularly maximum size, will not change significantly during a surveillance program.

Specific Aim 3: To determine if EGD measures of GIST size correlate well with EUS measures of GIST size.

Hypothesis: EGD measures of GIST size will correlate well with EUS measured of GIST size.

Prospective Database of Gastrointestinal Stromal Cell Tumors (GISTs)

Northwestern University

Washington University School of Medicine

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Chromosome Abnormalities in Chronic Myeloid Leukemia (CML) on Imatinib. GIST Patients on Imatinib	NCT00461929	Chronic Myeloid... Gastrointestina... Chromosome Abno...	bone marrow asp...	18 Years -	University Health Network, Toronto
Chromosome Abnormalities in Chronic Myeloid Leukemia (CML) on Imatinib. GIST Patients on Imatinib	NCT00461929	Chronic Myeloid... Gastrointestina... Chromosome Abno...	bone marrow asp...	18 Years -	University Health Network, Toronto
Prospective Database of Gastrointestinal Stromal Cell Tumors (GISTs)	NCT02147145	Gastrointestina... Foregut Subepit...		18 Years -	Washington University School of Medicine
Prospective Database of Gastrointestinal Stromal Cell Tumors (GISTs)	NCT02147145	Gastrointestina... Foregut Subepit...		18 Years -	Washington University School of Medicine
Chromosome Abnormalities in Chronic Myeloid Leukemia (CML) on Imatinib. GIST Patients on Imatinib	NCT00461929	Chronic Myeloid... Gastrointestina... Chromosome Abno...	bone marrow asp...	18 Years -	University Health Network, Toronto

Spots Global Cancer Trial Database for gastrointestinal stromal cell tumors