Targeting of sall4 for the treatment and diagnosis of...

A - Human Necessities – 61 – K

Patent

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A61K 39/395 (2006.01)

Patent

CA 2631312

The present invention discloses nucleic acids, proteins, and antibodies for SALL4 (including isoforms SALL4A, SALL4B, and SALL4C), a zinc finger transcriptional factor. Further, methods are disclosed which demonstrate that constitutive expression of SALL4 increases leukemogenic potential in cells of model animal systems. Moreover, constitutive expression of select isoforms (e.g., SALL4B) in transgenic mice demonstrate that these animals develop myelodysplastic syndrome (MDS)-like signs and symptoms, including subsequent acute myeloid leukemia (AML), which is transplantable. The disclosure also provides methods for identifying and purifying embryonic stem cells, adult stem cells, cancer stem cells, including leukemia stem cells, methods for identifying substances which bind to and/or modulate SALL4, methods for diagnosing MDS in a subject, and methods of treating a subject presenting MDS.

La présente invention concerne des acides nucléiques, des protéines et des anticorps pour SALL4 (y compris les isoformes SALL4A, SALL4B et SALL4C), un facteur de transcription à doigts de zinc. L'invention se rapporte en outre à des méthodes démontrant que l'expression constitutive de SALL4 augmente le potentiel leucémigène dans les cellules de systèmes animaux modèles. Par ailleurs, l'expression constitutive d'isoformes sélectionnées (par ex., SALL4B) dans des souris transgéniques démontre que ces animaux développent des signes et des symptômes de type syndrome myélodysplasique (SMD), y compris une leucémie myéloïde (LMA) subséquente, qui est transplantable. L'invention se rapporte en outre à des méthodes destinées à identifier et purifier des cellules souches embryonnaires, des cellules souches adultes, des cellules souches cancéreuses, y compris des cellules souches leucémiques, des méthodes destinées à diagnostiquer une SMD chez un sujet, ainsi que des méthodes destinées à traiter un sujet présentant une SMD.

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