Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Dalle, Iman Abou; Jabbour, Elias; Short, Nicholas J.; Ravandi, Farhad

doi:10.1007/s11864-019-0603-z

Cited by 58 publications

(40 citation statements)

References 56 publications

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“…Consequently, all of the scientific community is now working to find effective diagnostic tests and therapeutic approaches. Recently, a Dutch group started to treat COVID-19 pneumonitis with imatinib, a TKI already employed in CML ( 60 ), Ph+ ALL ( 61 ), and gastrointestinal stromal tumor (GIST) ( 62 ). The hypothesis that imatinib could be effective also in COVID-19 was based on some previous experimental observations done in SARS and MERS models where imatinib was able to block the virus entrance into human host cells ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

Tyrosine Kinase Inhibitors Play an Antiviral Action in Patients Affected by Chronic Myeloid Leukemia: A Possible Model Supporting Their Use in the Fight Against SARS-CoV-2

et al. 2020

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SARS-CoV-2 is the viral agent responsible for the pandemic that in the first months of 2020 caused about 400,000 deaths. Among compounds proposed to fight the SARS-CoV-2-related disease (COVID-19), tyrosine kinase inhibitors (TKIs), already effective in Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) and chronic myeloid leukemia (CML), have been proposed on the basis of their antiviral action already demonstrated against SARS-CoV-1. Very few cases of COVID-19 have been reported in Ph+ ALL and in CML Italian cohorts; authors suggested that this low rate of infections might depend on the use of TKIs, but the biological causes of this phenomenon remain unknown. In this study, the CML model was used to test if TKIs would sustain or not the viral replication and if they could damage patient immunity. Firstly, the infection and replication rate of torquetenovirus (TTV), whose load is inversely proportional to the host immunological control, have been measured in CML patients receiving nilotinib. A very low percentage of subjects were infected at baseline, and TTV did not replicate or at least showed a low replication rate during the follow-up, with a mean load comparable to the measured one in healthy subjects. Then, after gene expression profiling experiments, we found that several "antiviral" genes, such as CD28 and IFN gamma, were upregulated, while genes with "proviral" action, such as ARG-1, CEACAM1, and FUT4, were less expressed during treatment with imatinib, thus demonstrating that TKIs are not detrimental from the immunological point of view. To sum up, our data could offer some biological explanations to the low COVID-19 occurrence in Ph+ ALL and CML patients and sustain the use of TKIs in COVID-19, as already proposed by several international ongoing studies.

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Section: Discussionmentioning

confidence: 99%

Tyrosine Kinase Inhibitors Play an Antiviral Action in Patients Affected by Chronic Myeloid Leukemia: A Possible Model Supporting Their Use in the Fight Against SARS-CoV-2

et al. 2020

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“…The introduction of tyrosine kinase inhibitors (TKIs), such as imatinib, has improved the prognosis of this B-ALL subset. However, development of resistance to TKIs is still an unresolved issue [119,120]. At variance with B-ALL, no consensus genetic classification with either prognostic or therapeutic implications has not yet been reached for T-ALL.…”

Section: Upr Involvement In Allmentioning

confidence: 99%

The Unfolded Protein Response: A Novel Therapeutic Target in Acute Leukemias

Martelli

Paganelli

Chiarini

et al. 2020

Cancers

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The unfolded protein response (UPR) is an evolutionarily conserved adaptive response triggered by the stress of the endoplasmic reticulum (ER) due, among other causes, to altered cell protein homeostasis (proteostasis). UPR is mediated by three main sensors, protein kinase RNA-like endoplasmic reticulum kinase (PERK), activating transcription factor 6α (ATF6α), and inositol-requiring enzyme-1α (IRE1α). Given that proteostasis is frequently disregulated in cancer, UPR is emerging as a critical signaling network in controlling the survival, selection, and adaptation of a variety of neoplasias, including breast cancer, prostate cancer, colorectal cancer, and glioblastoma. Indeed, cancer cells can escape from the apoptotic pathways elicited by ER stress by switching UPR into a prosurvival mechanism instead of cell death. Although most of the studies on UPR focused on solid tumors, this intricate network plays a critical role in hematological malignancies, and especially in multiple myeloma (MM), where treatment with proteasome inhibitors induce the accumulation of unfolded proteins that severely perturb proteostasis, thereby leading to ER stress, and, eventually, to apoptosis. However, UPR is emerging as a key player also in acute leukemias, where recent evidence points to the likelihood that targeting UPR-driven prosurvival pathways could represent a novel therapeutic strategy. In this review, we focus on the oncogene-specific regulation of individual UPR signaling arms, and we provide an updated outline of the genetic, biochemical, and preclinical therapeutic findings that support UPR as a relevant, novel target in acute leukemias.

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“…In those patients positive for BCL-ABL1, the use of tyrosine kinase inhibitors has been used in combination with chemotherapy, although with the small number of cases, the effect of prognosis is not known [29,30].…”

Section: Discussionmentioning

confidence: 99%

Common B-cell acute lymphoblastic leukaemia in a 70-year-old woman presenting 2 years after carboplatin-taxane radiotherapy for endometrial cancer

Murray

Orrego

López

et al. 2019

ecancer

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Therapy-related acute lymphoblastic leukaemia (t-ALL) is a poorly defined entity and is not featured in the World Health Organization classification as a distinct clinical entity from acute lymphoblastic leukaemia (ALL), thus differing from therapy-related acute myeloid leukaemia and myelodysplasia. We present a case of tALL occurring 18 months after treatment for metastatic endometrial cancer with a regimen of carboplatin, paclitaxel and radiotherapy. The patient presented with severe pancytopenia and diagnosed with common-B ALL, and the cytogenetic analysis showed a previously unreported deletion in chromosome 19 (q13.1) in 100% of the blast cells. The patient declined further therapy and died 1 month later. This rare but serious side effect of chemo-radiotherapy should be considered when deciding on treatment options for gynaecological cancers.

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Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Cited by 58 publications

References 56 publications

Tyrosine Kinase Inhibitors Play an Antiviral Action in Patients Affected by Chronic Myeloid Leukemia: A Possible Model Supporting Their Use in the Fight Against SARS-CoV-2

Tyrosine Kinase Inhibitors Play an Antiviral Action in Patients Affected by Chronic Myeloid Leukemia: A Possible Model Supporting Their Use in the Fight Against SARS-CoV-2

The Unfolded Protein Response: A Novel Therapeutic Target in Acute Leukemias

Common B-cell acute lymphoblastic leukaemia in a 70-year-old woman presenting 2 years after carboplatin-taxane radiotherapy for endometrial cancer

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