The use of hydroxyurea pretreatment in chronic myeloid leukemia in the current tyrosine kinase inhibitor era

Kockerols, Camille C B; Geelen, Inge G.P.; Levin, Mark‐David; Janssen, Jeroen; Dinmohamed, Avinash G.; Hoogendoorn, Mels; Cornelissen, Jan J.; Westerweel, Peter E.

doi:10.3324/haematol.2021.280501

Cited by 6 publications

(4 citation statements)

References 7 publications

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“…A recent study suggested that undetectable transcript levels by droplet digital PCR predicts TFR success. 48 While digital PCR can reach up to 6 log reduction depth, the PCR assay used in the central lab for the present study had a limit of detection of 5.5 log reduction. We indirectly confirmed this finding as the absence of detectable BCR::ABL1 transcript levels below 5.5 log reduction was associated with a higher chance of TFR success.…”

Section: Discussionmentioning

confidence: 75%

“…Those patients with any detectable transcript levels between MR4 and MR5.4 ( n = 6) showed a 0% TFR2 rate at 6 months, while those with undetectable transcript levels (5.5 log reduction or deeper; n = 28) had a 28.6% TFR2 rate at 6 months ( p = 0.047, HR 2.759). A recent study suggested that undetectable transcript levels by droplet digital PCR predicts TFR success 48 . While digital PCR can reach up to 6 log reduction depth, the PCR assay used in the central lab for the present study had a limit of detection of 5.5 log reduction.…”

Section: Discussionmentioning

confidence: 76%

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Final report of TKI discontinuation trial with dasatinib for the second attempt of treatment‐free remission after failing the first attempt with imatinib: Treatment‐free Remission Accomplished by Dasatinib (TRAD) study

Perusini,

Novitzky‐Basso,

Atenafu

et al. 2023

Br J Haematol

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SummaryMultiple studies have reported a significant treatment‐free remission (TFR) rate of 50%–60% in patients with chronic myeloid leukaemia (CML) who discontinue tyrosine kinase inhibitor (TKI) therapy. However, the remaining half of these patients still require re‐initiation of TKI therapy for leukaemia control. It remains unclear if TKI drugs should be switched for re‐therapy in patients who failed the first TFR (TFR1) attempt. Our study attempted to determine whether dasatinib therapy after TFR1 failure post‐imatinib discontinuation could improve the likelihood of TFR2. Of 59 patients who lost molecular response after imatinib discontinuation for TFR1, 55 patients (93.2%) were treated with dasatinib, of whom 49 (89.1%) regained MR4.5 or deeper response, with a median time of 1.85 months to achieve MR4.5. Dasatinib was discontinued in 35 patients for TFR2 attempt, of whom 26 patients (74.28%) lost MMR and 6 (17.14%) MR4. Risk factor analysis for the TFR2 after dasatinib discontinuation suggested three significant factors: (1) doubling time of BCR::ABL1 transcript following TFR1 attempt, (2) rapid regaining of molecular response following dasatinib therapy and (3) undetectable BCR::ABL1 transcript prior to TFR2 attempt. The present study showed that dasatinib does not increase the TFR2 rate in general, but a selected group of patients could benefit from this approach.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 76%

Final report of TKI discontinuation trial with dasatinib for the second attempt of treatment‐free remission after failing the first attempt with imatinib: Treatment‐free Remission Accomplished by Dasatinib (TRAD) study

Perusini,

Novitzky‐Basso,

Atenafu

et al. 2023

Br J Haematol

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“…In addition, the in vitro ubiquitin experiment demonstrates that RRM2 is degraded by Cdh1‐mediated polyubiquitination in G2/M phase 28 . Several RRM2 inhibitors have been used in clinical practices or trials, such as hydroxyurea, triapine, and GTI2040 29–32 . However, these drugs have not been clinically applied to NSCLC.…”

Section: Discussionmentioning

confidence: 99%

“…28 Several RRM2 inhibitors have been used in clinical practices or trials, such as hydroxyurea, triapine, and GTI2040. [29][30][31][32] However, these drugs have not been clinically applied to NSCLC. Therefore, there is an urgent need to explore more potential targets that regulate RRM2 protein level or function.…”

Section: Discussionmentioning

confidence: 99%

USP12 promotes nonsmall cell lung cancer progression through deubiquitinating and stabilizing RRM2

Chen

Xue

Liu

et al. 2023

Molecular Carcinogenesis

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RRM2 is the catalytic subunit of ribonucleotide reductase (RNR), which catalyzes de novo synthesis of deoxyribonucleotide triphosphates (dNTPs) and plays critical roles in cancer cell proliferation. RRM2 protein level is controlled by ubiquitination mediated protein degradation system; however, its deubiquitinase has not been identified yet. Here we showed that ubiquitin‐specific peptidase 12 (USP12) directly interacts with and deubiquitinates RRM2 in non‐small cell lung cancer (NSCLC) cells. Knockdown of USP12 causes DNA replication stress and retards tumor growth in vivo and in vitro. Meanwhile, USP12 protein levels were positively correlated to RRM2 protein levels in human NSCLC tissues. In addition, high expression of USP12 was associated with poor prognosis in NSCLC patients. Therefore, our study reveals that USP12 is a RRM2 regulator and targeting USP12 could be considered as a potential therapeutical strategy for NSCLC treatment.

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Incidental diagnosis of pediatric chronic myeloid leukemia in the setting of acute appendicitis: A case report and review of management strategies

Wang,

Gigliotti,

Gough

et al. 2024

Pediatric Blood & Cancer

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The use of hydroxyurea pretreatment in chronic myeloid leukemia in the current tyrosine kinase inhibitor era

Abstract: Not available.

Cited by 6 publications

References 7 publications

Final report of TKI discontinuation trial with dasatinib for the second attempt of treatment‐free remission after failing the first attempt with imatinib: Treatment‐free Remission Accomplished by Dasatinib (TRAD) study

Final report of TKI discontinuation trial with dasatinib for the second attempt of treatment‐free remission after failing the first attempt with imatinib: Treatment‐free Remission Accomplished by Dasatinib (TRAD) study

USP12 promotes nonsmall cell lung cancer progression through deubiquitinating and stabilizing RRM2

Incidental diagnosis of pediatric chronic myeloid leukemia in the setting of acute appendicitis: A case report and review of management strategies

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