BCR-ABL rearrangement is not detectable in essential thrombocythemia

Essential thrombocythemia (ET) is a chronic myeloproliferative disorder (MPD) characterized by an elevated thrombocytosis, an increased number of megakaryocytes with dismegakaryopoiesis in the bone marrow, and no identifiable underlying primary causes. According to the current diagnostic criteria of the Polycythemia Vera Study Group (PVSG), ET is lacking in features diagnostic for other MPDs, including Philadelphia chromosome (Ph). Karyotypic anomalies are rare and not specific, and the clonality is controversial; so this disorder remains a diagnosis of exclusion, and the identification of subgroups of patients at risk for progression to leukemia is quite difficult. Recently, some authors reported a BCR-ABL transcript positivity in about a half of 25 Ph− ET cases.1 Here we investigated the presence of the molecular counterpart of the Ph chromosome in a larger series of ET patients with a longer follow-up. We investigated 112 white patients (44 males, 68 females; median age, 56 years, range 23 to 98 years) diagnosed with ET following the criteria of the PVSG. Cytogenetic analyses were performed, at diagnosis and prior to any treatment, in all patients using conventional banding methods. Molecular studies for the detection of chimeric messengers BCR-ABL, coding for p190 and p210 proteins, were performed by “nested” reverse transcriptase–polymerase chain reaction (RT-PCR) on total RNAs extracted from bone marrow mononuclear cells In our group of 112 patients at cytogenetic examination, no one showed the t(9;22) translocation, at diagnosis. The RT-PCR studies for BCR-ABL transcripts showed the chimeric product (b3a2 type) only in 1 patient (0.89%). The clinical and hematologic features remained unchanged in the majority of patients, with few exceptions; 8 patients showed a disease transformation . Two patients died from blastic crisis and two from cerebral stroke, from 6 to 10 years after diagnosis. Whether an MPD with marked thrombocythosis and expressing theBCR-ABL transcripts might be considered a variant form of ET or of CML has raised controversies for several years. The results of our observations on a larger series of patients with ET showed the absence of the BCR-ABL rearrangements in this disease. The only BCR-ABL+ patient of our series (0.89%), on which we already reported,10 is probably an unusual case of CML at thrombocythemic onset and long survival, a case that finally progressed to acute leukemia. The longer follow-up of our patients (median 62.79 months for the 80.35% of our series of patients, compared with medians 22.5 and 37 months in Blickstein et al1 and Singer et al,9 respectively) allowed us to document a disease course more consistent with the natural history of ET than that of CML. Our suggestion is that true ET does not carry the Ph anomaly that, instead, might characterize the CML variant forms with thrombocythemia.