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Gene expression molecular signature identified in chronic myeloid leukemia

07-27-2006

According to a study from Germany, gene expression profiling of CD34+ cells identifies a molecular signature of chronic myeloid leukemia (CML) blast crisis.

"Despite recent success in the treatment of early-stage disease, blastic phase (BP) of CML that is characterized by rapid expansion of therapy-refractory and differentiation-arrested blasts, remains a therapeutic challenge," wrote C. Zheng and colleagues, University of Heidelberg.

They continued, "The development of resistance upon continuous administration of imatinib mesylate is associated with poor prognosis pointing to the need for alternative therapeutic strategies and a better understanding of the molecular mechanisms underlying disease progression."

"To identify transcriptional signatures that may explain pathological characteristics and aggressive behavior of BP blasts, we performed comparative gene expression profiling on CD34+ Ph+ cells purified from patients with untreated newly diagnosed chronic phase CML (CP, n=11) and from patients in BP (n=9) using Affymetrix oligonucleotide arrays.

"Supervised microarray data analysis revealed 114 differentially expressed genes (p<10-4), 34 genes displaying more than two-fold transcriptional changes when comparing CP and BP groups. While 24 of these genes were down-regulated, 10 genes, especially suppressor of cytokine signalling 2 (SOCS2), CAMPATH-1 antigen (CD52), and four human leukocyte antigen-related genes were strongly overexpressed in BP. Expression of selected genes was validated by real-time-polymerase chain reaction and flow cytometry," wrote the researchers.

The investigators concluded, "Our data suggest the existence of a common gene expression profile of CML-BP and provide new insight into the molecular phenotype of blasts associated with disease progression and high malignancy."

Zheng and colleagues published the results of their research in Leukemia (Gene expression profiling of CD34+ cells identifies a molecular signature of chronic myeloid leukemia blast crisis. Leukemia, 2006;20(6):1028-1034).

For additional information, contact W. Seifarth, University of Heidelberg, Fak Klin Med Mannheim, Medicine Klin 3, Wiesbadener Str 7-11, D-68305 Mannheim, Germany.

The publisher of the journal Leukemia can be contacted at: Nature Publishing Group, Macmillan Building, 4 Crinan St., London N1 9XW, England.

Keywords: Mannheim, Germany, Blast Crisis, Chronic Myeloid Leukemia, Expression Profiling, Gene Expression, Oligonucleotide Microarrays, CD34+ Cell.

This article was prepared by Cancer Gene Therapy Week editors from staff and other reports. Copyright 2006, Cancer Gene Therapy Week via NewsRx.com.