TKI dasatinib monotherapy for a patient with Ph‐like ALL bearing <i>ATF7IP/PDGFRB</i> translocation

Kobayashi, Kenichiro; Miyagawa, Naoyuki; Mitsui, Kazumasa; Matsuoka, Masaki; Kojima, Yasuko; Takahashi, Hiroyuki; Ootsubo, Kaori; Nagai, J.; Ueno, Hikaru; Ishibashi, Tatsuro; Sultana, Sara; Okada, Yôko; Akimoto, Shingo; Okita, Hajime; Matsumoto, Kimikazu; Goto, Hiroaki; Kiyokawa, Nobutaka; Ohara, Akira

doi:10.1002/pbc.25327

Cited by 57 publications

(32 citation statements)

References 15 publications

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“…ABL class fusions, involving ABL1, ABL2, CSF1R, and PDGRFB, are present in approximately 10% of Ph-like B-ALL and are targetable with ABL tyrosine kinase inhibitors such as Dasatinib [14,32,83,88]. Clinical trials testing Dasatinib in patients harboring these lesions are also using Ruxolitinib if there is JAK/STAT signaling pathway activation and are detailed in the section above titled JAK/STAT pathway targets.…”

Section: Abl Inhibitionmentioning

confidence: 99%

The Current Genomic and Molecular Landscape of Philadelphia-like Acute Lymphoblastic Leukemia

Shiraz

Payne

Muffly

2020

IJMS

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Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) is a high-risk B-cell Acute Lymphoblastic Leukemia (B-ALL) characterized by a gene expression profile similar to Ph-positive B-ALL but lacking the BCR-ABL1 translocation. The molecular pathogenesis of Ph-like B-ALL is heterogenous and involves aberrant genomics, receptor overexpression, kinase fusions, and mutations leading to kinase signaling activation, leukemogenic cellular proliferation, and differentiation blockade. Testing for the Ph-like signature, once only a research technique, is now available to the clinical oncologist. The plethora of data pointing to poor outcomes for this ALL subset has triggered investigations into the role of targeted therapies, predominantly involving tyrosine kinase inhibitors that are showing promising results.

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Section: Abl Inhibitionmentioning

confidence: 99%

The Current Genomic and Molecular Landscape of Philadelphia-like Acute Lymphoblastic Leukemia

Shiraz

Payne

Muffly

2020

IJMS

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“…Jellemző genetikai rendellenessé-geik szerint a Ph-like betegek további kategóriákba oszthatók, azok szerint pedig molekuláris inhibitorokkal kezelhetők [42]. Az ABL-osztályba (ABL1, ABL2, PDGFRB, CSF1R) tartozó génátrendeződéssel rendelkező kemoterápiarefrakter betegek TKI-kezelése (dazatinib) kiváló eredményeket hozott [46]. A JAK2/EPOR átrendeződések és a Ph-like ALL-esek körülbelül felében meglévő CRLF2-eltérések a JAK2 aktiváló mutációjával asszociáltak, így ezekben az esetekben a JAK2-inhibitor ruxolitinib hatékonynak bizonyul [47].…”

Section: Molekuláris Patogenezis éS úJ Patogenetikai Alapú Kezelési unclassified

Új és hagyományos irányok a gyermekkori akut lymphoblastos leukaemia biológiájában és ellátásában

et al. 2018

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Az utóbbi néhány évtized klinikai előrelépéseinek köszönhetően az akut lymphoblastos leukaemiás (ALL-) gyermekek nagy hányada ma az első vonalbeli kemoterápiás protokollok révén meggyógyul, és küzd a kortársak közé való visszatérés problémáival. Azonban a betegek jelentős részénél súlyos akut és késői terápiás mellékhatásokkal kell szá-molni. Emellett egyes betegcsoportok (például MLL-átrendeződéssel, hipodiploiditással, IKZF1-mutációval vagy korai prekurzor T-sejtes fenotípussal jellemezhető betegek) túlélése messze elmarad az átlagostól. Számukra nyújta-nak jobb klinikai kilátásokat az újabb betegellátási stratégiák: komplex géndiagnosztika, molekulárisan célzott daganatgátlás, immunonkológia és sejtterápia. Harminc feletti azon géneknek a száma, amelyek eltéréseit azonosították leukaemiás lymphoblastokban, és patobiológiai szerepük is valamennyire ismert. Ismerünk olyan betegcsoportot is (Philadelphia-like B-sejtes ALL), ahol a génexpressziós profilalkotás ad alapot a tirozin-kináz-inhibitorok használatá-nak. A leukaemiaasszociált immunfenotípus diagnóziskori áramlási citometriás meghatározásával és genetikai mód-szerekkel követhetővé vált a minimális residualis betegség. A blastfelszíni differenciációs klaszterek (elsősorban CD19, CD20 és CD22 a malignus B-sejteken) epitópjai monoklonális antitestekkel támadhatók. Fokozható a tumorellenes immunitás is, részben szintén a tumor sejtfelszíni markereinek (bispecifikus T-sejt-kapcsolóknál, kiméra antigénrecep-torú T-sejtes terápiánál), részben pedig a tumorspecifikus immunsejteknek (immunellenőrzőpont-gátlóknál) a kihasználása révén. A jelen közleményben áttekintést kívánunk adni a patogenetika új irányairól, a betegségkövetés modern módjairól és a célzott citotoxicitás innovatív lehetőségeiről biztató klinikai tanulmányok alapján. Orv Hetil. 2018; 159(20): 786-797. Keywords: akut lymphoblastos leukaemia, patogenezis, toxicitás, immunterápia, célzott molekuláris terápia New and traditional directions in the biology and management of childhood acute lymphoblastic leukemiaOwing to clinical trials and improvement over the past few decades, the majority of children with acute lymphoblastic leukemia (ALL) survive by first-line chemotherapy and combat with the problems of returning to community. However, many patients may have severe acute or late therapeutic side effects, and the survival rate in some groups (e.g., patients with MLL rearrangements, hypodiploidy, IKZF1 mutation or early precursor T cell phenotype) is far behind the average. Innovative strategies in medical attendance provide better clinical outcomes for them: complete gene diagnostics, molecularly targeted anticancer treatment, immuno-oncology and immune cell therapy. The number of genes with identified alterations in leukemic lymphoblasts is over thirty and their pathobiologic role is only partly clear. There are known patient groups where the use of specific drugs is based on gene expression profiling (e.g., tyrosine kinase inhibitors in Philadelphia-like B-cell ALL). The continuous assessment of min...

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“…Thus, the Ph‐like feature may not necessarily be enriched in relapsed ALL, but it is important to note that some cases of relapsed ALL might have these targetable genetic alterations. There have been several case reports that showed that tyrosine kinase inhibitors successfully induced remission in refractory Philadelphia chromosome‐negative ALL patients, including a T‐ALL patient …”

Section: Therapeutic Strategy For Relapsed Allmentioning

confidence: 99%

“…There have been several case reports that showed that tyrosine kinase inhibitors successfully induced remission in refractory Philadelphia chromosome-negative ALL patients, including a T-ALL patient. [58][59][60][61] Bortezomib is a selective inhibitor of the ubiquitin-proteasome pathway. Proteasome inhibition affects many cellular processes, including inhibition of NF-kb, which is postulated to be involved in the anti-cancer effects of bortezomib.…”

Section: Molecularly Targeted Drugsmentioning

confidence: 99%

Childhood relapsed acute lymphoblastic leukemia: Biology and recent treatment progress

Goto

2015

Pediatrics International

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Acute lymphoblastic leukemia (ALL) is the most frequent cancer in children. Despite remarkable improvement in the prognosis of childhood ALL over the past few decades, the treatment of relapsed ALL is still challenging. The prognosis of first ALL relapse is associated with time of relapse after initial therapy, sites of relapse, and immunophenotype. More recently, response to treatment, which is evaluated by assessment of minimal residual disease (MRD), has been found to be clinically significant in relapsed ALL as well as in the initially diagnosed disease. Utilizing these factors, risk-oriented treatment stratification for first ALL relapse has been established. In the standard-risk group for first ALL relapse, intensification of conventional ALL-type therapy can provide a cure in approximately 70% of patients. It is important to assess MRD after reinduction therapy to determine the indications for stem cell transplantation in the standard-risk group. In contrast, no standardized therapy has been established for the high-risk group, which accounts for more than half of relapsed ALL patients. Recent studies have shed light on the clonal origin of relapsed ALL, which usually exists as a minor subclone at the time of initial diagnosis. Clonal selection and evolution take place during chemotherapy, resulting in distinct genetic and epigenetic characteristics of relapsed ALL, some of which are linked to drug resistance, a common and problematic feature of ALL after relapse. To overcome resistance to standard ALL-type therapy, and considering the heterogeneous biological background of high-risk relapsed ALL, innovative therapies using new agents are necessary.Key words acute lymphoblastic leukemia, children, relapse.Acute lymphoblastic leukemia (ALL) is the most frequent malignant disease in children. Over the past few decades, marked improvement in treatment of childhood ALL has been achieved via better understanding of tumor biology and progress of supportive therapy. The cure rate of childhood ALL in developed countries is now 85-90%, 1-3 and childhood ALL represents a success model in cancer therapy. A total of 10-15% of patients with childhood ALL, however, do relapse. ALL after relapse is no longer a manageable disease. Because of its dominance in childhood cancers, relapsed ALL is still the main cause of cancer death in children. 4 Unlike the progress in the treatment of initial-diagnosis pediatric ALL, the prognosis of relapsed ALL has not improved over the years.5 A systematic approach, however, made mainly by study groups in Europe and North America, has established clinical prognostic factors that enabled the development of risk-oriented therapy for relapsed ALL. 6 Response to therapy, as measured by assessment of minimal residual disease (MRD), has been found to have clinical significance in the treatment stratification of ALL after relapse as well as for the initially diagnosed disease. 7 Using such an approach, standardized therapy for lower-risk ALL relapse is being established. Recent progres...

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TKI dasatinib monotherapy for a patient with Ph‐like ALL bearing ATF7IP/PDGFRB translocation

Cited by 57 publications

References 15 publications

The Current Genomic and Molecular Landscape of Philadelphia-like Acute Lymphoblastic Leukemia

The Current Genomic and Molecular Landscape of Philadelphia-like Acute Lymphoblastic Leukemia

Új és hagyományos irányok a gyermekkori akut lymphoblastos leukaemia biológiájában és ellátásában

Childhood relapsed acute lymphoblastic leukemia: Biology and recent treatment progress

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