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Role for proteomics in identifying hematologic malignancies

Researchers have identified a set of biomarkers that could help clinicians identify a group of hematologic malignancies known as myelodysplastic syndromes ( MDS ), which affect approximately 300,000 individuals worldwide and often progress to acute myeloid leukemia.

Reported in the Proceedings of the National Academy of Sciences ( PNAS ) the findings point to a possible new diagnostic method for these malignancies, which occur when blood cells remain in an immature stage within the bone marrow and never sufficiently develop into the mature cells necessary for proper hematologic functioning.

The study was led by researchers at Beth Israel Deaconess Medical Center ( BIDMC ) and Heinrich Heine University in Duesseldorf, Germany.

Currently, a bone marrow biopsy is the only definitive means available to diagnose myelodysplastic syndromes.
Therefore, a clinical study has tested whether serum proteomic profiling might be used to identify biomarkers for myelodysplastic syndromes.

Researchers used a combination of two technologies, protein fractionation and mass spectrometry, to create proteome profiles from the serum of 218 patients ( representing clinical trial participants from both the MDS Study Group in Duesseldorf and from BIDMC ). Through these profiles, the investigators were able to successfully distinguish between cases of myelodysplastic syndromes, healthy control subjects and cases of non-MDS-related cytopenias.

" Rather than uncovering a single biomarker, we were able to identify a protein signature, which reproducibly identified MDS patients among three separate and distinct patient cohorts," explains Libermann. " Since many patients with autoimmune disorders are treated with cytotoxic drugs such as Azathioprine or Methotrexate, they become cytopenic and may be suspected of having myelodysplastic syndromes. By using this new profile, the need for bone marrow biopsies might also be reduced among this patient population."

In the second part of the study, the authors identified two separate chemokines – CXCL4 and CXCL7 – the first such molecular biomarkers for advanced myelodysplastic syndromes.

" Proteomic profiling, using in-depth mass spectrometry, follows in the footsteps of genomics and represents a critical next step in understanding the pathophysiology of diseases," says Libermann. " This study demonstrated for the first time that proteomic profiling can be used for biomarker discovery and diagnostic evaluation of hematologic malignancies, an important step in refining the diagnosis and, eventually, the treatment of this devastating malignancy."

Source: Beth Israel Deaconess Medical Center, 2007