Leukaemia ‘firsts’ in cancer research and treatment

Greaves, M. Nature Reviews Cancer. 16, 163–172 (2016)

Our understanding of cancer biology has been radically transformed over recent years with a more realistic grasp of its multilayered cellular and genetic complexity. These advances are being translated into more selective and effective treatment of cancers and, although there are still considerable challenges, particularly with drug resistance and metastatic disease, many patients with otherwise lethal malignancies now enjoy protracted remissions or cure.

One largely unheralded theme of this story is the extent to which new biological insights and novel clinical applications have their origins with leukaemia and related blood cell cancers, including lymphoma. In this Timeline article, I review the remarkable and ground-breaking role that studies in leukaemia have had at the forefront of this progress.


Image source: Greaves, M.

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Predictive staircase to leukemia revealed by researchers

Researchers detail in a new article how they have been able to fingerprint myelodysplastic syndromes, a state for blood cells that turns into acute myeloid leukemia cancer in approximately 30 percent of patients.

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In the paper published by the scientific journal Cancer Cell, the researchers detail how they have been able to fingerprint myelodysplastic syndromes (MDS), a state for blood cells that turns into acute myeloid leukemia (AML) cancer in approximately 30% of patients. The study demonstrates that early and accurate prediction of this aggressive cancer is possible.

AML is the most common type of leukemia in adults, and about 1,300 Canadians are expected to develop the disease each year.

Bhatia’s research team found when they deleted one version of the important GSK-3 gene, the other version of the gene became active but remained non-cancerous. However, when the second version of the gene was also deleted, AML cancer began.

To test this, Bhatia’s team collaborated with Italian researchers at the University of Bologna to apply these initial findings to human blood samples that had been previously collected from patients with MDS, some of whom eventually developed AML. McMaster researchers did a retroactive study, and demonstrated that gene expression analysis of patient blood samples was accurate in predicting which patients would develop AML and which would not.

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Ibrutinib superior to traditional chemotherapy in untreated chronic leukemia patients

Burger, J. et al. New England Journal of Medicine, 2015.

A multi-center, international, randomized, Phase III study of older untreated patients with chronic lymphocytic leukemia (CLL) demonstrated that ibrutinib, a kinase inhibitor, is significantly more effective than traditional chemotherapy with chlorambucil.

The study, which followed 269 patients, revealed a 24-month overall survival rate of 97.8 percent for patients taking ibrutinib versus 85.3 percent for those on chlorambucil. Minor adverse effects were reported.

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Method to prevent lethal bone marrow transplant complication discovered

Analysis of research article by ScienceDaily

Bone_marrow_WBC.JPGOriginal article: S. N. Furlan et al. Transcriptome analysis of GVHD reveals aurora kinase A as a targetable pathway for disease prevention. Science Translational Medicine, 2015; 7 (315): 315ra191 DOI: 10.1126/scitranslmed.aad3231#

A Seattle Children’s Research Institute lab has discovered a genetic pathway that can be targeted with existing drugs to prevent graft-versus-host disease (GVHD), a common and deadly complication of bone marrow transplants. The results of their work were published in the journal Science Translational Medicine.

In patients with GVHD, newly transplanted T cells from the bone marrow graft attack the transplant recipient’s body. Over 10,000 people in the United States receive bone marrow transplants each year for leukemia, other non-malignant blood conditions and autoimmune diseases. About 50-70 percent of bone marrow transplant patients will acquire GVHD. Of those who develop the most severe form, up to half will die.

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Leukemia tumor suppressor identified

A protein-coding gene called hnRNP K has been identified as a tumor suppressor for acute myeloid leukemia (AML), a finding that could be important for investigating how best to target treatment of a blood cancer striking mostly older individuals.

Study results were published in the Sept. 24 issue of Cancer Cell:  Post, S  et al. hnRNP K Is a Haploinsufficient Tumor Suppressor that Regulates Proliferation and Differentiation Programs in Hematologic Malignancies. Cancer Cell, September 2015