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Blood, 1 July 2007, Vol. 110, No. 1, pp. 375-379.
Prepublished online as a Blood First Edition Paper on March 15, 2007; DOI 10.1182/blood-2006-12-062125.
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NEOPLASIA
Brief Report
Leukemic blasts in transformed JAK2-V617F–positive myeloproliferative disorders are frequently negative for the JAK2-V617F mutation.
Alexandre Theocharides1,2,
Marjorie Boissinot3,
François Girodon4,
Richard Garand5,
Soon-Siong Teo1,
Eric Lippert6,
Pascaline Talmant5,
Andre Tichelli7,
Sylvie Hermouet3,5, and
Radek C. Skoda1
1 Department of Research, Experimental Hematology, University Hospital Basel, Switzerland;
2 Division of Clinical Hematology, University Hospital Basel, Switzerland;
3 Institut National de la Santé et de la Recherche Médicale Unité 601, Institut de Biologie, Nantes, France;
4 Laboratoire d'Hématologie, Centre Hospitalier Universitaire (CHU) de Dijon, France;
5 Laboratoire d'Hématologie, CHU de Nantes, France;
6 Laboratoire d'Hématologie, CHU de Bordeaux, France;
7 Division of Diagnostic Hematology, University Hospital Basel, Switzerland
To study the role of the JAK2-V617F mutation in leukemic transformation, we examined 27 patients with myeloproliferative disorders (MPDs) who transformed to acute myeloid leukemia (AML). At MPD diagnosis, JAK2-V617F was detectable in 17 of 27 patients. Surprisingly, only 5 of 17 patients developed JAK2-V617F–positive AML, whereas 9 of 17 patients transformed to JAK2-V617F–negative AML. Microsatellite analysis in a female patient showed that mitotic recombination was not responsible for the transition from JAK2-V617F–positive MPD to JAK2-V617F–negative AML, and clonality determined by the MPP1 polymorphism demonstrated that the granulocytes and leukemic blasts inactivated the same parental X chromosome. In a second patient positive for JAK2-V617F at transformation, but with JAK2-V617F–negative leukemic blasts, we found del(11q) in all cells examined, suggesting a common clonal origin of MPD and AML. We conclude that JAK2-V617F–positive MPD frequently yields JAK2-V617F–negative AML, and transformation of a common JAK2-V617F–negative ancestor represents a possible mechanism.

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