The long-term clinical implications of clonal chromosomal abnormalities in newly diagnosed chronic phase chronic myeloid leukemia patients treated with imatinib mesylate

Lee, Sung‐Eun; Choi, Soo Young; Bang, Jae Seung; Kim, Soohyun; Jang, Eun Chul; Byeun, Ji-Young; Park, Jin Eok; Jeon, Hye-Rim; Oh, Yun Jeong; Kim, Myungshin; Kim, Dong-Wook

doi:10.1016/j.cancergen.2012.09.003

Cited by 23 publications

(16 citation statements)

References 24 publications

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“…Both monosomy 7 and del (7p) are of the additional chromosomal abnormalities and they associated with adverse prognostic factors in CML patients treated with IM as a frontline therapy [19,20].…”

Section: Discussionmentioning

confidence: 99%

A novel cytogenetic abnormality r(7)(::p11.2->q36.3::) in a Philadelphia-positive chronic myeloid leukemia case

Achkar¹,

Wafa²,

Aljapawe³

et al. 2013

CRCM

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The so-called Philadelphia (Ph) chromosome is present in more than 90% of chronic myeloid leukemia (CML) cases. It results in juxtaposition of the 5' part of the BCR gene on chromosome 22 and the 3' part of the ABL1 gene on chromosome 9. An additional acquired monosomy 7 or deletion of 7q is associated with poor prognosis in a variety of myeloid disorders. Here we report a novel Ph chromosome positive CML case with a ring chromosome 7 [r(7)]. Immunophenotyping was compatible with CML, although 4.5% of total leucocytes appeared like acute myelogeneous leukemia (AML) subtype M2. The r(7) was characterized in detail by array-proven multicolor banding (aMCB), the latter being of enormous significance to characterize breakpoint regions in detail. Underlying mechanisms and prognostic are discussed, as ring chromosomes are rare cytogenetic abnormalities in hematopoietic malignancies.

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Section: Discussionmentioning

confidence: 99%

A novel cytogenetic abnormality r(7)(::p11.2->q36.3::) in a Philadelphia-positive chronic myeloid leukemia case

Achkar¹,

Wafa²,

Aljapawe³

et al. 2013

CRCM

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“…Općenito je prihvaćeno da ne postoji statistički značajna razlika u postizanju KCgO-a među pacijentima s varijantnom i klasičnom Ph translokacijom 8,[17][18][19] . Razlike postoje u nekim istraživanjima između prognostičkog značaja pacijenata s varijantnom i klasičnom translokacijom [15][16] . Zaključak ovog istraživanja je da ne postoji razlika u postizanju KCgO-a kod pacijenata liječenih IM-om ili NI-om u te dvije skupine pacijenata.…”

Section: Zaključakunclassified

Učestalost varijantne translokacije kod pacijenata s novodijagnosticiranom kroničnom mijeloičnom leukemijom (KML) u hrvatskoj populaciji

Švabek¹,

Josipović

2020

Med. Flum. (Online)

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Cilj: Obilježje kronične mijeloične leukemije (KML) je hibridni BCR-ABL gen nastao kao posljedica recipročne translokacije između kromosoma 9 i 22, čime se stvara Philadelphia (Ph) kromosom. Klasičnu translokaciju t(9;22) ima 90 % pacijenata, dok ostalih 5 – 10 % ima varijantnu translokaciju koja uključuje više kromosoma, izuzev kromosoma 9 i 22. Cilj ovog istraživanja je odrediti postotak pacijenata s novodijagnosticiranim KML-om koji imaju varijantnu translokaciju te postotak kompletnog citogenetičkog odgovora (KCgO) pacijenata s varijantnom translokacijom u usporedbi s pacijentima koji imaju klasičnu t(9;22). Materijali i metode: U istraživanje je uključena koštana srž (KS) 177 pacijenata s novodijagnosticiranim KML-om. Za analizu Ph kromosoma koristio se kariogram kao klasična citogenetska analiza i fluorescentna in situ hibridizacija (FISH) kao molekularna citogenetska analiza. Rezultati: Varijantna translokacija dokazana je kod 14 pacijenata u razdoblju od 5 godina i 3 mjeseca, dok 163 pacijenta ima klasičnu translokaciju t(9;22). Zaključak: Postotak pacijenata s varijantnom translokacijom u istraživanju slaže se s rezultatima istraživanja u svijetu. Ne postoji statistički značajna razlika u postizanju KCgO-a kod pacijenata s varijantnom translokacijom t(9;22) u usporedbi s KCgO-om pacijenata s klasičnom translokacijom.

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“…In the study by Weisberg et al . . Dp210 cells were transfected with firefly luciferase and then injected into Nu/Nu NCR‐nude mice.…”

Section: Alternative Strategiesmentioning

confidence: 99%

“…Two studies published in 2012 investigated inhibition of CXCR4 with plerixafor in combination with either nilotinib (78) or imatinib and dasatinib (147). In the study by Weisberg et al (32). Dp210 cells were transfected with firefly luciferase and then injected into Nu/Nu NCR-nude mice.…”

Section: Immunotherapeutic Targeting In CMLmentioning

confidence: 99%

Do we need more drugs for chronic myeloid leukemia?

Holyoake

Helgason

2014

Immunological Reviews

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The introduction of protein tyrosine kinase inhibitors (TKIs) in 1998 transformed the management of chronic myeloid leukemia (CML), leading to significantly reduced mortality and improved 5 year survival rates. However, the CML community is faced with several clinical issues that need to be addressed. Ten to 15% of CML patients are diagnosed in advanced phase, and small numbers of chronic phase (CP) cases experience disease progression each year during treatment. For these patients, TKIs induce only transient responses and alternative treatment strategies are urgently required. Depending on choice of first line TKI, approximately 30% of CML CP cases show suboptimal responses, due to a combination of poor compliance, drug intolerance, and drug resistance, with approximately 50% of TKI-resistance caused by kinase domain mutations and the remainder due to unknown mechanisms. Finally, the chance of successful treatment discontinuation is on the order of only 10-20% related to disease persistence. Disease persistence is a poorly understood phenomenon; all CML patients have functional Philadelphia positive (Ph+) stem and progenitor cells in their bone marrows and continue to express BCR-ABL1 by DNA PCR, even when in very deep remission and following treatment discontinuation. What controls the maintenance of these persisting cells, whether it is necessary to fully eradicate the malignant clone to achieve cure, and how that might be approached therapeutically are open questions.

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The long-term clinical implications of clonal chromosomal abnormalities in newly diagnosed chronic phase chronic myeloid leukemia patients treated with imatinib mesylate

Cited by 23 publications

References 24 publications

A novel cytogenetic abnormality r(7)(::p11.2->q36.3::) in a Philadelphia-positive chronic myeloid leukemia case

A novel cytogenetic abnormality r(7)(::p11.2->q36.3::) in a Philadelphia-positive chronic myeloid leukemia case

Učestalost varijantne translokacije kod pacijenata s novodijagnosticiranom kroničnom mijeloičnom leukemijom (KML) u hrvatskoj populaciji

Do we need more drugs for chronic myeloid leukemia?

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The long-term clinical implications of clonal chromosomal abnormalities in newly diagnosed chronic phase chronic myeloid leukemia patients treated with imatinib mesylate

Cited by 23 publications

References 24 publications

A novel cytogenetic abnormality r(7)(::p11.2-&gt;q36.3::) in a Philadelphia-positive chronic myeloid leukemia case

A novel cytogenetic abnormality r(7)(::p11.2-&gt;q36.3::) in a Philadelphia-positive chronic myeloid leukemia case

Učestalost varijantne translokacije kod pacijenata s novodijagnosticiranom kroničnom mijeloičnom leukemijom (KML) u hrvatskoj populaciji

Do we need more drugs for chronic myeloid leukemia?

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A novel cytogenetic abnormality r(7)(::p11.2->q36.3::) in a Philadelphia-positive chronic myeloid leukemia case

A novel cytogenetic abnormality r(7)(::p11.2->q36.3::) in a Philadelphia-positive chronic myeloid leukemia case