Karyotype findings and molecular analysis of the bcr gene rearrangement supplementing the histologic classification of chronic myeloproliferative disorders.
BACKGROUND
Histologic examination of bone marrow is important in establishing diagnoses among chronic myeloproliferative disorders (CMPD). Only a few studies, however, have compared cytogenetic or molecular genetic findings to histopathology in CMPD. Diverging results on the presence of the Ph1-translocation in patients with myelofibrosis have been reported.


METHODS
Cytogenetic studies and molecular analysis of the bcr gene were performed in bone marrow cells of patients with CMPD simultaneously with histopathologic examination of plastic-embedded bone marrow biopsies.


RESULTS
The Ph1-chromosome was found in 120/128 (93%) cases with histopathologic diagnosis of chronic myeloid leukemia (CML), including a notable proportion of cases with an increase of megakaryocytes and/or myelofibrosis; the latter was associated with a significant increase of chromosome aberrations, in addition to Ph1. Among those additional changes in myelofibrosis of Ph1-positive CML were del (13q) and t(1;11) in one case each. A bcr gene rearrangement was detected in 92% (24/26) of the CML cases examined. All other groups of CMPD, comprising cases of myelofibrosis and unclassifiable cases, were Ph1-negative by both cytogenetics (n = 102) and molecular analysis (n = 18). Karyotype changes associated with myelofibrosis in various CMPD concerned mainly balanced translocations involving 1p36 and 11q11, deletions of 5q13-34, 3p, 11q23, 13(q12,q22), and 20q12 as well as gain of 1q and trisomy 3, 8, 19, or 21. In histologically unclassifiable CMPD, karyotyping provided additional information for the differential diagnosis.


CONCLUSIONS
The correlation of cytogenetic findings and histopathologic features is helpful in confirming or supporting histopathologic diagnoses and in characterizing new marker chromosomes in CMPD.
Werner
M
M
Pathologisches Institut, Medizinischen Hochschule, Hannover, Germany.
Nolte
M
M
Kaloutsi
V
V
Buhr
T
T
Kausche
F
F
Georgii
A
A
D000368:Aged; D002452:Cell Count; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D002874:Chromosome Mapping; D002908:Chronic Disease; D015321:Gene Rearrangement; D006801:Humans; D007621:Karyotyping; D008533:Megakaryocytes / Q000473:pathology; D008875:Middle Aged; D008967:Molecular Biology; D009196:Myeloproliferative Disorders / Q000235:genetics* / Q000473:pathology*; D055728:Primary Myelofibrosis / Q000473:pathology; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051562:Proto-Oncogene Proteins c-bcr; D014178:Translocation, Genetic
D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr