Every case of essential thrombocythemia should be tested for the Philadelphia chromosome

Abstract

Essential thrombocythemia (ET) and chronic myelogenous leukemia (CML) usually present with distinctive features. Citing experience with cases that overlap, the Polycythemia Vera Study Group recommends that negative tests for the Philadelphia chromosome be obtained before diagnosing ET. We describe two young women presenting with features absolutely typical for ET, including extreme thrombocytosis, no leukocytosis, no basophilia, no peripheral immature cells, and no splenomegaly. Severe thrombotic complications ensued: multiple cerebrovascular thromboemboli, pulmonary emboli, and miscarriage in one and myocardial infarction in the other. By 4 years, both developed leukocytosis, extreme basophilia, and circulating blasts, typical of accelerated CML. Cytogenetic studies were then performed, revealing the Philadelphia chromosome. Imatinib produced rapid clearing of blasts and basophils, but one woman later succumbed after allogeneic bone marrow transplant and the other has not achieved a major cytogenetic response. We conclude that CML can present in identical fashion as ET. The mandate for routine Philadelphia chromosome testing is magnified by the availability of targeted therapy and its greater efficacy in early stage disease. Am.

Thrombocytosis and STAT5 activation in chronic myelogenous leukaemia are not associated withJAK2V617F or calreticulin mutations

“…In conclusion, this study validates the importance of determining BCR-ABL1 status in cases of marked thrombocytosis clinically suspected to be ET 3. An accurate diagnosis of CML can help avoid unnecessary antithrombotic therapy and allow rapid initiation of effective TKI therapy.…”

“…Among MPNs, marked thrombocytosis, especially in the absence of prominent leucocytosis, is typically associated with ET. Some cases of ET can mimic CML with thrombocytosis (CML-T), and a final diagnosis of CML may come as a surprise when conventional cytogenetic and/or molecular studies reveal an unanticipated t(9;22)(q34;q11.2) and/or BCR-ABL1 fusion 3. The concept of Philadelphia chromosome-positive (Ph + ) or BCR-ABL1 -positive ET has been debated in the literature,4–6 but the World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Hematopoietic and Lymphoid Tissues resolved the issue in 2001 by establishing BCR-ABL1 as both a disease-defining criterion for the diagnosis of CML and an exclusionary criterion for the diagnosis of ET, PV and PMF 7.…”

Pathogenetic insight and prognostic information from standard and molecular cytogenetic studies in the BCR-ABL-negative myeloproliferative neoplasms (MPNs)

“…47 Finally, it has been proposed that cytogenetic analysis should be undertaken in all cases of ET, as rarely CML may present with an identical phenotype. [48][49][50] Although such presentations are rare, the success of tyrosine kinase inhibitors in CML makes it important that such a diagnosis is not missed. 51 Finally, cytogenetic analysis of haematopoietic colonies suggests that, at least in some patients, the disease can arise at the multipotent stem cell level.…”

Genotypic and phenotypic classification of cancer: How should the impact of the two diagnostic approaches best be balanced?

“…The latter situation was dealt with by reclassifying the BCR-ABL1-positive ETand IBMF-cases as CML; evidently, the new pathogenetic insights were so impressive that the genetic criteria had gained priority over the hematologic ones. The circumstance that imatinib treatment had been shown to have the same beneficial effect in Ph-positive disease regardless of whether it had originally been called CML or ET (Rice and Popat, 2005), of course contributed to this decision. For the acute leukemias with t(9;22), on the other hand, the separate naming practices were retained and one continued to talk about CML (now by definition always Ph-positive) as well as Ph-positive AML and ALL instead of a common Ph-positive leukemia.…”