Management of chronic myeloid leukemia in blast crisis

Saußele, Susanne; Silver, Richard T.

doi:10.1007/s00277-015-2324-0

Cited by 63 publications

(45 citation statements)

References 64 publications

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“…This likely due to a small population of highly quiescent chronic myelogenous leukemia cells, which are insensitive to the tyrosine kinase inhibitors and they are believed to be early leukemia progenitor cells [6–8]. However, the precise molecular events resulting in cell resistance to therapeutic drugs have not been completely elucidated [8, 9]. …”

Section: Introductionmentioning

confidence: 99%

“…Although new tyrosine inhibitor derivatives have been reported to have higher efficiencies in the treatment of chronic myelogenous leukemia; a reduced number of the patients will progress to the accelerated phase of the disease, the most aggressive illness form, namely blast crisis [9, 10] and eventually these patients may die. Therefore, the use of some polyphenolic compounds as supplements or adjuvants for chemotherapy in chronic myelogenous leukemia and other types of leukemia has been extensively researched, for example, curcumin and its chemical derivatives.…”

Section: Introductionmentioning

confidence: 99%

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A Subpopulation of the K562 Cells Are Killed by Curcumin Treatment after G2/M Arrest and Mitotic Catastrophe

et al. 2016

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Curcumin is extensively investigated as a good chemo-preventive agent in the development of many cancers and particularly in leukemia, including treatment of chronic myelogenous leukemia and it has been proposed as an adjuvant for leukemia therapies. Human chronic myeloid leukemia cells (K562), were treated with 20 μM of curcumin, and we found that a subpopulation of these cells were arrested and accumulate in the G2/M phase of the cell cycle. Characterization of this cell subpopulation showed that the arrested cells presented nuclear morphology changes resembling those described for mitotic catastrophe. Mitotic cells displayed abnormal chromatin organization, collapse of the mitotic spindle and abnormal chromosome segregation. Then, these cells died in an apoptosis dependent manner and showed diminution in the protein levels of BCL-2 and XIAP. Moreover, our results shown that a transient activation of the nuclear factor κB (NFκB) occurred early in these cells, but decreased after 6 h of the treatment, explaining in part the diminution of the anti-apoptotic proteins. Additionally, P73 was translocated to the cell nuclei, because the expression of the C/EBPα, a cognate repressor of the P73 gene, was decreased, suggesting that apoptosis is trigger by elevation of P73 protein levels acting in concert with the diminution of the two anti-apoptotic molecules. In summary, curcumin treatment might produce a P73-dependent apoptotic cell death in chronic myelogenous leukemia cells (K562), which was triggered by mitotic catastrophe, due to sustained BAX and survivin expression and impairment of the anti-apoptotic proteins BCL-2 and XIAP.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Subpopulation of the K562 Cells Are Killed by Curcumin Treatment after G2/M Arrest and Mitotic Catastrophe

et al. 2016

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“…Clinical resistance to IM for CML patients has been attributed to several mechanisms, and the dominant mechanism appears to be the acquisition of point mutations in the ABL kinase domain (KD) (30%-90% of patients de-velop resistance) that lead to altered affinity for IM by the BCR-ABL1 protein [6,7]. However, due to IM treatment resistance, a proportion of CML patients easily progress to blast crisis phase (blastic transformation may be myeloid, lymphoid, or undifferentiated/mixed), which is an advanced stage of CML disease progression that contributes to the expansion of primitive cells and not mature granulocytes [8][9][10]. To date, greater than 90 ABL gene mutants have been described [6,11].…”

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confidence: 99%

Characteristics of the TCR Vβ repertoire in imatinib-resistant chronic myeloid leukemia patients with ABL mutations

Lai

et al. 2015

Sci. China Life Sci.

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Diversity in the T cell receptor (TCR) repertoire provides a miniature defense ability for the T cell immune system that may be related to tumor initiation and progression. Understanding the T cell immune status of leukemia patients is critical for establishing specific immunotherapies. Previous studies have reported abnormal TCR repertoires and clonally expanded TCR V T cells in chronic myeloid leukemia in chronic phase (CP-CML). In this study, we investigated the distribution and clonality of the TCR V repertoire in 4 cases with imatinib-resistant CML in blast crisis (BC-CML) with abelson murine leukemia viral oncogene homolog 1 (ABL1) kinase domain mutations (KDMs). Examination of TCR V expression and clonality was performed by reverse transcription-polymerase chain reaction (RT-PCR) and GeneScan analysis. Significantly skewed TCR V repertoires were observed in BC-CML patients with different KDMs, and 4 to 8 oligoclonally expanded TCR V subfamilies could be identified in each sample. Intriguingly, a relatively highly expanded V9 clone with the same length as complementarity-determining region 3 (CDR3) (139 bp) was found in all three CML patients in lymphoid blast crisis (LBC-CML) who had different KDMs, but the clone was not detected in the only CML patient in myeloid blast crisis (MBC-CML). In conclusion, restricted TCR V repertoire expression and decreased clone complexity was a general phenomenon observed in the BC-CML patients with different KDMs, indicating the T-cell immunodeficiency of these patients. In addition, clonally expanded V9 T cell clones may indicate a specific immune response to leukemia-associated antigens in LBC-CML patients.T cell repertoire, chronic myeloid leukemia, blast crisis, imatinib resistance, BCR-ABL mutation Citation:

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“…[2] Once BC happens, the management depends on the type of leukemia (myeloid or lymphoid) and if they successfully achieve CR or not. [3] Allogeneic stem cell transplantation (Allo-HSCT) may be the only curly therapy for the patients, [4] but as influenced by a donor source and recipient status, it is successful in only a minority of CML-BC patients. [5] This patient was diagnosed with CP and was given IM 400.…”

Section: Discussionmentioning

confidence: 99%

The third-time chronic myeloid leukemia in lymphoblastic crisis with ABL1 kinase mutation induced by decitabine, dexamethason combined with nilotinib and dasatinib

Wang

Qiao

Zhu

et al. 2016

Journal of Translational Internal Medicine

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Blast crisis (BC) is the major remaining challenge in the management of chronic myeloid leukemia (CML). The prognosis of the BC patient who carries ABL kinase mutation is very poor. One patient, with lymphoid CML-BC third time, was detected with T315A/F359I/M244V compound mutation by direct sequencing after treatment with tyrosine kinase inhibitions three years. The patient was treated with decitabine, dexamethasone, in combination with nilotinib and dasatinib. Then this patient received a complete hematologic response and cytogenetic response after two cycles of treatment.

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Management of chronic myeloid leukemia in blast crisis

Cited by 63 publications

References 64 publications

A Subpopulation of the K562 Cells Are Killed by Curcumin Treatment after G2/M Arrest and Mitotic Catastrophe

A Subpopulation of the K562 Cells Are Killed by Curcumin Treatment after G2/M Arrest and Mitotic Catastrophe

Characteristics of the TCR Vβ repertoire in imatinib-resistant chronic myeloid leukemia patients with ABL mutations

The third-time chronic myeloid leukemia in lymphoblastic crisis with ABL1 kinase mutation induced by decitabine, dexamethason combined with nilotinib and dasatinib

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