Chronic myeloid leukemia: 2014 update on diagnosis, monitoring, and management

Abstract

Disease overview: Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm with an incidence of 1–2 cases per 100,000 adults, and accounts for ∼15% of newly diagnosed cases of leukemia in adults. Diagnosis: CML is characterized by a balanced genetic translocation, t(9;22)(q34;q11.2), involving a fusion of the Abelson oncogene (ABL) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a BCR‐ABL fusion oncogene, which in turn translates into a Bcr‐Abl oncoprotein. Frontline therapy: Three tyrosine kinase inhibitors (TKIs), imatinib, nilotinib, and dasatinib have been approved by the US Food and Drug Administration for the first‐line treatment of patients with newly diagnosed CML in chronic phase (CML‐CP). Clinical trials with second generation TKIs reported significantly deeper and faster responses; their impact on long‐term survival remains to be determined. Salvage therapy: For patients who fail frontline therapy, second‐line options include second and third generation TKIs. Although second and third generation TKIs are potent and specific BCR‐ABL TKIs, they exhibit unique pharmacological profiles and response patterns relative to different patient characteristics, such as patients comorbidities, disease stage, and BCR‐ABL mutational status. Patients who develop the T315I “gatekeeper” mutation display resistance to all currently available TKIs except ponatinib. Allogeneic transplantation remains an important therapeutic option for CML‐CP who have failed at least 2 TKIs, and for all patients in advanced phase disease. Am. J. Hematol. 89:547–556, 2014. © 2014 Wiley Periodicals, Inc.

Nilotinib rapidly reverses breakpoint cluster region-Abelson oncogene fusion gene and M244V mutations in a patient with chronic myelogenous leukemia: A case report

“…Dasatinib is favored when patients have Y253H, E255K/V or F359C/V mutations in BCR-ABL. By contrast, nilotinib is more effective when V299L or F317L mutations are present (2). Despite this evidence, it remains unclear how the M244V mutation to the BCR-ABL fusion protein should affect the choice of treatment.…”

“…The US Food and Drug Administration has approved three tyrosine kinase inhibitors (TKIs), imatinib, nilotinib and dasatinib, as first-line treatments for patients diagnosed with CML in the chronic phase (CML-CP) (2)(3)(4)(5). Imatinib mesylate, otherwise known as Gleevec ® (Novartis Pharmaceuticals Corp., East Hanover, NJ, USA), was the first of the TKIs to receive approval; however, 20-40% of patients receiving imatinib as a first-line therapy are likely to eventually require an alternative treatment, due to intolerance or resistance to imatinib (5).…”

Successful Third Hematopoietic Stem Cell Transplantation for Blast Crisis of Chronic Myeloid Leukemia After Two Times of Graft Failure

“…7.8 Based on these reports, conditioning regimen of first CBT was not suspected to be a factor of graft failure. [1][2][3] If the blood concentration of BU is below its effective concentration, frequency of graft failure would increase. Area under the blood concentration-time curve (AUC) of intravenous BU administration is more stable than preoral BU.…”

“…1 A graft failure is one of the crucial complications in allo-HSCT. If it occurs, the most of the patients run their fatal course.…”

An overview of chronic myeloid leukemia and its animal models

“…Chronic myeloid leukemia (CML) is a cancer occurring in one to two of 100,000 adults, and comprises nearly 15% of the cases of adult leukemia [1]. CML is distinguished by clonal expansion of primitive pluripotent stem cells without the loss of their capability to differentiate into myeloid cells, and by a dramatic increase in proliferation of granulocytic cells that have the capacity to differentiate [2].…”