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Identification of latent myeloproliferative disease in patients with Budd‐Chiari syndrome using X‐chromosome inactivation patterns and in vitro erythroid colony formation
Author(s) -
Acharya J.,
Westwood N. B.,
Sawyer B. M.,
Messinezy M.,
Burroughs A. K.,
Mehta A. B.,
Pearson T. C.
Publication year - 1995
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.1995.tb00703.x
Subject(s) - phosphoglycerate kinase , biology , x inactivation , x chromosome , restriction fragment length polymorphism , locus (genetics) , monoclonal , microbiology and biotechnology , cytogenetics , genetics , pathology , chromosome , genotype , monoclonal antibody , antibody , medicine , gene
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 [BstX1 RFLP]) and M27β (an anonymous locus DXS255 at Xp11.22 [Pst1 RFLP]) were used to study methylation patterns. All 7 patients were heterozygous using M27β 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 M27β. Two patients who had aberrant patterns of X inactivation with M27β 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.