Tricks of the trade for the appropriate management of newly diagnosed acute promyelocytic leukemia

Sanz, Miguel Á.; Tallman, Martin S.; Lo‐Coco, Francesco

doi:10.1182/blood-2004-09-3475

Cited by 114 publications

(119 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Dexamethasone is the current mainstay of the management of patients with RAS (40). Interestingly, Lam et al (17) demonstrated that this drug induces stiffening of acute lymphatic leukemia cells.…”

Section: Discussionmentioning

confidence: 99%

The regulatory role of cell mechanics for migration of differentiating myeloid cells

Lautenschläger

Paschke²,

Schinkinger³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

223

207

View full text Add to dashboard Cite

Migration of cells is important for tissue maintenance, immune response, and often altered in disease. While biochemical aspects, including cell adhesion, have been studied in detail, much less is known about the role of the mechanical properties of cells. Previous measurement methods rely on contact with artificial surfaces, which can convolute the results. Here, we used a non-contact, microfluidic optical stretcher to study cell mechanics, isolated from other parameters, in the context of tissue infiltration by acute promyelocytic leukemia (APL) cells, which occurs during differentiation therapy with retinoic acid. Compliance measurements of APL cells reveal a significant softening during differentiation, with the mechanical properties of differentiated cells resembling those of normal neutrophils. To interfere with the migratory ability acquired with the softening, differentiated APL cells were exposed to paclitaxel, which stabilizes microtubules. This treatment does not alter compliance but reduces cell relaxation after cessation of mechanical stress six-fold, congruent with a significant reduction of motility. Our observations imply that the dynamical remodeling of cell shape required for tissue infiltration can be frustrated by stiffening the microtubular system. This link between the cytokeleton, cell mechanics, and motility suggests treatment options for pathologies relying on migration of cells, notably cancer metastasis.acute promyelocytic leukemia ͉ cytoskeleton ͉ microtubules ͉ optical stretcher ͉ paclitaxel

show abstract

Section: Discussionmentioning

confidence: 99%

The regulatory role of cell mechanics for migration of differentiating myeloid cells

Lautenschläger

Paschke²,

Schinkinger³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

223

207

View full text Add to dashboard Cite

show abstract

“…However, confirmation and extension of these results in a larger patient cohort may be difficult to achieve, as advances in the treatment of APL have reduced the relapse rate to as low as 10%. 30 Also, the recent incorporation of ATRA into all phases of treatment will further limit relapse sample availability without proximate ATRA treatment, and salvage therapy is more frequently being initiated at the time of molecular relapse rather than clinical relapse, 31 which proscribes facile, low-sensitivity screening for PML-RARa mutations. Nevertheless, we suggest that several questions merit exploration within the evolving APL treatment context.…”

Section: Discussionmentioning

confidence: 99%

Relapse of acute promyelocytic leukemia with PML-RARα mutant subclones independent of proximate all-trans retinoic acid selection pressure

et al. 2006

View full text Add to dashboard Cite

Relapse of acute promyelocytic leukemia (APL) following alltrans retinoic acid (ATRA) therapy has been associated with the acquisition of mutations in the high-affinity ATRA binding site in PML-RARa, but little information is available about the selection dynamics of the mutation-harboring subclones. In this study, 6/18 patients treated with sequential ATRA and chemotherapy on protocol INT0129 relapsed with complete replacement of the nonmutant pretreatment APL cell population by a PML-RARa mutant subclone. Two patients relapsed in proximity of ATRA treatment; however, in four patients there was a 6-48 month hiatus between the last ATRA treatment and relapse. The mutant subclones were not detectable in samples tested X3 months before relapse at X1 in 10 2 (10 À2 ) sensitivity. In one patient, a functionally weak mutation was detected at 10 À4 sensitivity before therapy but only limited pre-relapse enrichment of the mutant subclone was observed on subsequent ATRA therapy. These results indicate that proximate ATRA selection pressure is frequently not the main determinant for the emergence of strongly dominant PML-RARa mutant subclones and suggest that APL subclones harboring PMLRARa mutations are predisposed to the acquisition of secondary genetic/epigenetic alterations that result in a growth/ survival advantage.

show abstract

“…Cerca de 80 a 90% dos pacientes apresentam durante o diagnóstico alguma síndrome hemorrágica, sendo fatal em alguns pacientes durante o período de apresentação da doença; aproximadamente 3% morrem em conseqüência de hemorragia, antes do início do tratamento. A variante hipogranular encontra-se especificamente associada com risco elevado de morte precoce em decorrência de hemorragia (Avvisati et al,2001;Tallman et al,2005;Sanz et al, 2005;Arbuthnot, Wilde et al,2006).…”

Section: -Características Epidemiológicas Da Leucemia Promielocítica unclassified

“…Pacientes com características morfológicas sugestivas de LPA que não apresentam o rearranjo PML-RARα, ou alternativamente, pacientes cujo aspecto morfológico não leva à suspeita de LPA, porém possuem a alteração genética específica, têm sido descritos freqüentemente na literatura (Lo Coco et al,1999;Grimwade et al,2000;Lock et al, 2004). Por causa da diferença na eficácia do tratamento baseado no ATRA ser estritamente dependente do rearranjo genético presente nas células leucêmicas, a confirmação do mesmo é obrigatória durante o diagnóstico na LPA, levando a necessidade de um diagnóstico genético rápido e preciso (Lock et al,2004;Sanz et al,2005). (Grimwade, Lo Coco.,2002;Schoch et al, 2002;Zaccaria et al, 2002;Owatari et al, 2007).…”

Section: (Figura 8)unclassified

“…(Brockman et al, 2003;Wolff et al,2007). A grande vantagem dessa técnica é que, além da sua especificidade, sensibilidade aumentada e rapidez, pode ser utilizada tanto em cromossomo metafásico quanto interfásico, permitindo, com isso, a obtenção de resultados não só nos casos em que existe dificuldade em obter metáfases em número e qualidade necessários para análise, como também em um número variável de tipos de amostras (Grimwade, Lo Coco., 2002;Sanz et al,2005 Van Dongen et al, 2005).…”

Section: (Figura 8)unclassified

See 1 more Smart Citation

Avaliação da citogenética convencional e molecular em portadores de leucemia promielocítica aguda no Serviço de Hematologia do Hospital das Clínicas da Faculdade de Medicina da USP

Leal¹

View full text Add to dashboard Cite

Tricks of the trade for the appropriate management of newly diagnosed acute promyelocytic leukemia

Cited by 114 publications

References 43 publications

The regulatory role of cell mechanics for migration of differentiating myeloid cells

The regulatory role of cell mechanics for migration of differentiating myeloid cells

Relapse of acute promyelocytic leukemia with PML-RARα mutant subclones independent of proximate all-trans retinoic acid selection pressure

Avaliação da citogenética convencional e molecular em portadores de leucemia promielocítica aguda no Serviço de Hematologia do Hospital das Clínicas da Faculdade de Medicina da USP

Contact Info

Product

Resources

About