Hypereosinophilic syndrome with evolution to myeloproliferative disorder: temporal relationship to loss of Y chromosome and c-N-ras activation.
A case of hypereosinophilic syndrome is presented in which the patient was serially observed for 4 years. Transformation to a disorder resembling chronic myeloid leukemic (CML) occurred 36 months after diagnosis; at 42 months, blastic transformation and marrow failure ensued, leading to death. Marrow examination for histopathologic, cytogenetic, and molecular biologic analyses were performed during the eosinophilic, myeloproliferative, and blastic stages. These demonstrated ras activation by virtue of a codon 12 G to C transversion mutation, predicting for substitution of glycine by alanine; in addition, we observed Y chromosome loss late in the natural history of this illness, suggesting that these genetic lesions can play a role in the profound loss of myeloid differentiation characteristic of the accelerated phase commonly observed in myeloproliferative syndromes.
Needleman
S W
SW
Department of Medicine, University of Maryland Hospital, Baltimore 21201.
Mane
S M
SM
Gutheil
J C
JC
Kapil
V
V
Heyman
M R
MR
Testa
J R
JR
D000328:Adult; D001483:Base Sequence; D004273:DNA, Neoplasm / Q000302:isolation & purification; D004277:DNA, Single-Stranded / Q000138:chemical synthesis; D004802:Eosinophilia / Q000150:complications / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000209:etiology / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008969:Molecular Sequence Data; D009196:Myeloproliferative Disorders / Q000209:etiology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012729:Sex Chromosome Aberrations / Q000235:genetics; D013577:Syndrome; D013997:Time Factors; D014998:Y Chromosome
D004273:DNA, Neoplasm; D004277:DNA, Single-Stranded