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[Display omitted] • A split-type electrochemical DNA sensor using enzyme-linked DNA magnetic beads. • Duplex ligase chain reaction and OR logic gate are intergrated into this biosensor. • The electrochemical biosensor exhibits excellent performance in real sample assay. • This biosensor is promising for clinical application of chronic myelocytic leukemia. Detection of BCR/ABLp210 transcript levels, allowing for the early diagnosis of chronic myelocytic leukemia (CML) and its minimal residual disease (MRD) monitoring, plays a decisive role in the cure of CML. Herein, to realize the sensitive detection of BCR/ABLp210 transcript by electrchemical DNA (E-DNA) sensors in clinical samples, a split-type strategy using enzyme-linked DNA magnetic beads (MBs) was intelligently provided. Specifically, the utilization of magnetic separation makes the target recognition event separate from electrochemical measurements, avoiding the interference of complex matrices on the sensing interface. Besides, the MBs adopted as dispersible electrodes could improve mass transfer of target compared to that of a planar electrode. Consequently, the proposed E-DNA sensor combined with the ligation chain reaction (LCR) could achieve an exceptional performance with a low detection limit of 1 aM, a broad linear concentration range, and a remarkable specificity with a single-base resolution. Also, K562 cells in up to a 1000-fold excess of NB4 cells could be successfully detected by this E-DNA sensor. Finally, the integration of duplex LCR and OR logic gate into the E-DNA sensor has enabled the detection of e13a2/e14a2/both isoforms of BCR/ABLp210 transcript in a single assay in both newly diagnosed CML patients and those undergoing or having undergone treatment by tyrosine kinase inhibitors. Therefore, this method offers an alternative for the early diagnosis of CML and its MRD monitoring, and holds a huge potential of clinical translation due to its advantage of low cost, ease of miniaturization and generalizability. [ABSTRACT FROM AUTHOR]

Abstract: Activation-induced deaminase (AID), a cytidine deaminase, can accelerate the acquisition of BCR-ABL1 kinase domain mutations in human CML. In the present study, we investigated the expression of AID and Bcr-Abl in CML cells derived from 35 clinical patients. We found that both AID and Bcr-Abl were correlatively over-expressed in CML-LBC (lymphoid blast crisis) cells as compared with those in CML-CP (chronic phase) cells. AID expression was significantly decreased in CML-LBC cells after treated with arsenic trioxide, especially together with imatinib. We also observed satisfied therapy effects of As2O3 and imatinib on patients with CML blast crisis. These data suggest that decreasing AID expression in CML-LBC by As2O3 may be a promising approach to CML treatment. [Copyright &y& Elsevier]

Abstract: Within the past 10–15 years, major advances in therapy have strongly improved prognosis of patients with chronic myelocytic leukaemia (CML). We estimated trends in 5- and 10-year relative survival of patients developing CML after a previous malignancy in the United States from 1990–1994 to 2000–2004. Period analysis was employed to disclose recent developments with minimum delay. Overall, 5- and 10-year relative survival increased from 17.6% to 37.7% (p <0.0001) and from 7.6% to 23.8% (p <0.0001), respectively. Improvements were particularly strong in younger age groups. Prognosis of CML patients with previous malignancy no longer lags behind prognosis of patients with primary CML. [Copyright &y& Elsevier]

Abstract: There has been remarkable progress in our understanding of plasma cell dyscrasias and leukemias in recent years. New prognostic factors have come to light. Del(1)(p12) and t(4;14) confer poor prognoses on patients with myeloma. COX-2 positivity is associated with poorer progression-free and overall survival in myeloma patients and a role for COX-2 inhibitors in myeloma has been suggested. Thalidomide (400mg/day) and dexamethasone (20mg/m2 daily for 4 days) has emerged as first-line treatment for myelomas. Serious toxicities have been recognized, however. The thalidomide derivative, lenalidomide may be more active and less toxic than the parent compound and may replace it. Lenolidomide is also highly active against 5q-syndrome. Bortezomib is at least as active as thalidomide and less toxic, and the two drugs are not cross-resistant. Although marrow transplantation was the standard of care for newly diagnosed myeloma patients, recent prospective randomized studies cast doubt on its role. ZAP-70 and CD38 expression have major prognostic impact on outcome of chronic lymphocytic leukemia (CLL). The former may be a stronger predictor of the need for treatment than the presence of an unmutated IgV(H) gene. Although fludarabine is highly active in CLL, it may be associated with a higher number of second malignancies than are other treatments. Rituximab has major activity against CLL. However, at standard dose its effectiveness is limited by the fact that CD20 density is relatively low on CLL cells and circulating CD20 binds a significant fraction of administered drug. Either combining rituximab with other agents, or giving it in mega doses, which are safe and highly effective, can overcome these impediments. Imatinib has revolutionized the treatment of chronic phase chronic myelocytic leukemia (CML) and markedly decreased the number of allogeneic bone marrow transplants done for this neoplasm. However, the development of rapid resistance to the agent in blast crisis of CML or Philadelphia chromosome-positive acute lymphocytic leukemia gives the agent only a minor role in those diseases. More effective tyrosine kinase inhibitors currently under development may prove to be more useful in acute leukemias with the Philadelphia chromosome. Clofarabine is a successful new drug for acute myeloid leukemias of childhood and juvenile myelomonocytic leukemia. Drugs such as gemtuzumab ozogamicin, FLT3 inhibitors and farnesyl transferase inhibitors have been disappointing in acute leukemia. Histone deacetylase inhibition, especially in combination with proteasome inhibition, may be effective acute leukemia treatment. [Copyright &y& Elsevier]

We report a unique case of chronic myelocytic leukemia (CML) with the Philadelphia (Ph) chromosome. The patient obtained cytogenetic complete remission (CR) after treatment with interferon (IFN). When he transformed to acute lymphocytic leukemia (ALL), cytogenetic analysis showed that the karyotype was normal and fluorescence in situ hybridization (FISH) indicated that blast cells were Ph-negative. Immunophenotyping showed that the cells were CD34-positive and CD38-negative. Blast cells in his final stage were BCR/ABL rearrangement negative by reverse transcription polymerase chain reaction (RT-PCR). [Copyright &y& Elsevier]