Clinical Leukemia最新文献

The molecular pathogenesis of classic Philadelphia-negative myeloproliferative disorders (MPDs) has been greatly elucidated since the discovery of the JAK2V617F mutation in 2005. This abnormality is present in almost all patients with polycythemia vera and half of patients with essential thrombocythemia and primitive myelofibrosis. The mutation recapitulates many features of the human diseases in mouse models, is present in human hematopoietic stem cells, and is responsible for genomic instability. Nevertheless, many questions remain unanswered. How can 1 point mutation explain different disease phenotypes? Is JAK2V617F the sole event responsible for the JAK2V617F-positive MPDs? What is the cause of the disease in JAK2V617F-negative MPD? These questions are of particular interest at a time when different JAK2 inhibitors are being developed and used in clinical trials.

Telomeres and telomerase play an essential role in the regulation of the life span of human cells. Telomeres shorten progressively with each cell division, as well as in response to other causes, eventually leading to cell senescence and apoptosis. In contrast to most human somatic cells, T cells and certain B cells express the telomerase complex upon activation or stimulation, which compensates for telomere attrition to some degree. Telomerase reactivation has most likely evolved to extend the life span of certain T cells and B cells in order to adequately fulfill immune responses despite massive cellular expansion. Pathologic or abnormal reactivation of telomerase, however, is one of the hallmarks of cancer cells, and seems to be one of the key elements for developing T- and B-cell neoplasias. Manipulation of the telomere/telomerase complex in both normal and malignant T and B cells is highly attractive for therapeutic strategies.

Central nervous system (CNS) relapse in patients with acute promyelocytic leukemia (APL) is an uncommon event but increasingly reported in the all-trans-retinoic acid (ATRA) era. No standard of care for treating these patients currently exists. We describe 2 cases and review previous reports. Review of the medical literature revealed 61 additional patients, ranging in age from 3.5 to 73 years (median, 39 years). Leukocyte count at initial diagnosis ranged from 1.3 to 307 × 10⁹/L (median, 25.6 × 10⁹/L). Nearly all received ATRA first-line. Only 36% of the relapses were isolated to the CNS, and 86% of patients suffered from neurologic symptoms. Patients were treated with intrathecal chemotherapy alone, radiation alone, or both. In total, 75% of patients treated achieved CNS remission. The success rate of achieving CNS remission by combining radiation and intrathecal chemotherapy was 100%, superior to either modality alone (50% and 75%, respectively). All patients treated with craniospinal radiation were alive and free of disease at 1 year. Patients with APL should be fully evaluated at onset of new neurologic symptoms. Patients with APL with CNS relapse warrant systemic workup because most will not have isolated disease.

We evaluated the effect of anagrelide (ANA) in 9 of 22 patients with essential thrombocythemia (ET) who had a JAK2 V617F mutation and polycythemia vera (PV)–like disease. First, we observed a successful reduction of JAK2 mutation, which was associated with disappearance of PV-like phenotype. Second, we found that a level of JAK2 mutation < 50% was associated with a response to ANA similar to that of JAK2-negative patients. These data indicate that ANA may reverse the JAK2 mutational status and provide a better prognosis in patients with ET.

Granulocytic sarcomas are rare, extramedullary tumors composed of immature myeloid cells. Traditionally, these tumors present in patients with known leukemias; however, granulocytic sarcomas may present as an isolated finding in patients without known disease. As such, isolated granulocytic sarcomas may present a diagnostic challenge for clinicians taking care of the patient. Moreover, these tumors also create a therapeutic challenge for clinicians as they generally carry a poor prognosis and often have short-lived responses to systemic therapy with cytarabine-based chemotherapy. An improved understanding of the biology of granulocytic sarcomas may reveal targets accessible to some of the new biologically active agents being studied across oncology. This report of 3 usual presentations of granulocytic sarcomas and a brief review of the known pathophysiology reminds us that there is much work to do to improve outcomes for our patients.