Two myeloproliferative diseases in one patient - co-occurence of clones

Classical myeloproliferative diseases can be divided into Philadelphia chromosome-positive chronic myeloid leukemia and Philadelphia chromosome-negative myeloproliferative neoplasm. The driver mutations of the latter occur in the Janus kinase 2 or calreticulin genes. The coincidence of Philadelphia chromosome-negative and -positive myeloproliferative neoplasms in the same patient is exceptionally rare in the literature. During the long-term follow-up of our 120 patients with chronic myeloid leukemia, we investigated the clinical data of patients in whom Philadelphia chromosome-negative myeloproliferative disease was also confirmed. Philadelphia chromosome was detected by classical cytogenetic methods and/or fluorescence in situ hybridization. The amount of BCR-ABLI fusion RNA was monitored by quantitative real-time polymerase chain reaction. Mutations in the Janus kinase 2 and calreticulin genes were detected by quantitative allele-specific polymerase chain reaction and fragment analysis. The dynamics of disease development were inferred from the change in the amount of mutant clones over time and from the clinical data. We identified four cases carrying both Philadelphia chromosome and Janus kinase 2/calreticulin gene mutation. In some cases, competition between the clones, in other cases their co-occurrence in a common clone was observed. Isolated thrombocytosis at the time of diagnosis or persisting thrombocytosis during targeted therapy with good molecular response may call attention to the possibility of the co-occurrence of the two diseases. Co-occurrence of Philadelphia chromosome-positive and -negative myeloproliferative neoplasms is more frequent than the literature suggests. If the disease has an unusual appearance, the association of the two myeloproliferative dieseases may be suspected.