1. ¹Department of Haematology, Imperial College at Hammersmith Hospital, London, UK
2. ²Department of Haematology, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK
3. ³Glasgow Section of Experimental Haematology, Faculty of Medicine, University of Glasgow, Glasgow, UK
4. ⁴Division of Hematology-Oncology, Department of Internal Medicine, University of California at San Diego, San Diego, CA, USA
5. ⁵Department of Hematology-Oncology, Mayo Clinic Arizona, Scottsdale, AZ, USA
6. ⁶Department of Haematology, Guys Hospital Medical School, London, UK
7. ⁷Glasgow Section of Experimental Haematology, Faculty of Medicine, University of Glasgow, Glasgow, UK
8. ⁸The Ohio State University Comprehensive Cancer Center, Columbus OH, USA
9. ⁹Department of Research, University Hospital Basel, Basel, Switzerland
10. ¹⁰Department of Hematology, University of Florence, Florence, Italy

Correspondence: Professor JM Goldman, Department of Haematology, Imperial College London, Du Cane Road, London W12 0NN, UK. E-mail: jgoldman@imperial.ac.uk

Received 30 April 2009; Revised 10 May 2009; Accepted 19 May 2009; Published online 30 July 2009.

Abstract

Ph-positive chronic myeloid leukemia (CML) and Ph-negative chronic myeloproliferative diseases (MPDs), characterized in many cases by the presence of the JAK2^V617F mutation, have many features in common and yet also show fundamental differences. In this review, we pose five discrete and related questions relevant to both categories of hematological malignancy, namely: What are the mechanisms that underlie disease progression from a relatively benign or chronic phase? By what therapeutic methods might one target residual leukemia stem cells in CML? Is JAK2^V617F the original molecular event in MPD? What epigenetic events must have a role in dictating disease phenotype in MPDs? And finally, Will the benefits conferred by current or future JAK2^V617F inhibitors equal or even surpass the clinical success that has resulted from the use of tyrosine kinase inhibitors in CML? These and others questions must be addressed and in some cases should be answered in the foreseeable future.