IDENTIFICATION OF LATENT MYELOPROLIFERATIVE DISEASE IN PATIENTS WITH BUDD-CHIARI SYNDROME USING X-CHROMOSOME INACTIVATION PATTERNS AND IN-VITRO ERYTHROID COLONY FORMATION

Some patients with an early or latent myeloproliferative disorder (MPD ) present with Budd-Chiari syndrome (BCS, hepatic vein thrombosis). Ce ll culture analysis of erythroid progenitors (BFU-E) can be used to di scriminate primary from secondary MPD and examination of X-chromosome inactivation (in females) can be used to demonstrate clonality in neop lastic tissues. The present study used these techniques to examine whe ther 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 restric tion fragment length polymorphisms (RFLP) by differences in methylatio n between active and inactive chromosomes. Probes for two polymorphic loci, phosphoglycerate kinase (PGK, at Xq13.3 [BsiX1 RFLP]) and M27 be ta (an anonymous locus DXS255 at Xp11.22 [Pst 1 RFLP]) were used to st udy methylation patterns. All 7 patients were heterozygous using M27 b eta and 2/7 were also heterozygous using the PGK probe. Polyclonal pat terns of X-inactivation in granulocytes were demonstrated in 3/7, a sk ewed/monoclonal pattern in 1/7 and aberrant patterns in 3/7 using M27 beta. Two patients who had aberrant patterns of X inactivation with M2 7 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 wit h erythroid colony studies, can be used to assist in the diagnosis of an underlying MPD in BCS.