IDENTIFICATION OF LATENT MYELOPROLIFERATIVE DISEASE IN PATIENTS WITH BUDD-CHIARI SYNDROME USING X-CHROMOSOME INACTIVATION PATTERNS AND IN-VITRO ERYTHROID COLONY FORMATION.
EUR J HAEMATOL
315 - 321.
Some patients with an early or latent myeloproliferative disorder (MPD) present with Budd-Chiari syndrome (BCS, hepatic vein thrombosis). Cell culture analysis of erythroid progenitors (BFU-E) can be used to discriminate primary from secondary MPD and examination of X-chromosome inactivation (in females) can be used to demonstrate clonality in neoplastic tissues. The present study used these techniques to examine whether a group of 7 female patients who presented with BCS had evidence to support a diagnosis of MPD. Unilateral X-inactivation and therefore clonality can be studied in females heterozygous for X-linked restriction fragment length polymorphisms (RFLP) by differences in methylation between active and inactive chromosomes. Probes for two polymorphic loci, phosphoglycerate kinase (PGK, at Xq13.3 [BsiX1 RFLP]) and M27 beta (an anonymous locus DXS255 at Xp11.22 [Pst 1 RFLP]) were used to study methylation patterns. All 7 patients were heterozygous using M27 beta and 2/7 were also heterozygous using the PGK probe. Polyclonal patterns of X-inactivation in granulocytes were demonstrated in 3/7, a skewed/monoclonal pattern in 1/7 and aberrant patterns in 3/7 using M27 beta. Two patients who had aberrant patterns of X inactivation with M27 beta demonstrated a skewed/monoclonal pattern with PGK. The results of BFU-E growth patterns and clonality were entirely concordant in 5/6 patients. Thus X-chromosome inactivation patterns, in conjunction with erythroid colony studies, can be used to assist in the diagnosis of an underlying MPD in BCS.
|Title:||IDENTIFICATION OF LATENT MYELOPROLIFERATIVE DISEASE IN PATIENTS WITH BUDD-CHIARI SYNDROME USING X-CHROMOSOME INACTIVATION PATTERNS AND IN-VITRO ERYTHROID COLONY FORMATION|
|Keywords:||X-INACTIVATION PATTERNS, MYELOPROLIFERATIVE DISORDERS, BUDD-CHIARI SYNDROME, ERYTHROID COLONIES, FRAGMENT-LENGTH-POLYMORPHISMS, POLYMERASE CHAIN-REACTION, PORTAL-VEIN THROMBOSIS, HUMAN-TUMORS, CLONAL ORIGIN, METHYLATION PATTERNS, PRIMARY POLYCYTHEMIA, PROBE M27-BETA, DIAGNOSIS, GENE|
|UCL classification:||UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Centre for Cardiovascular Genetics
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