10 d'agost de 2018

Alterations in three genes in acute lymphoblastic leukaemia patients found to be a sign of better outcomes during treatment

A study led by Eulàlia Genescà of the Acute Lymphoblastic Leukaemia (ALL) Group has found that patients with altered number of copies in CDNKN2/ARF and CDNKN2B respond better to initial treatments and require bone marrow transplants less often.  The work is published in the Journal of Hematology and Oncology.

Acute lymphoblastic leukaemia affects the white blood cells; it occurs in adults and children and is the most common childhood cancer, often affecting children under five. It progresses rapidly and requires rapid treatment, which in most cases follows a standard protocol of chemotherapy followed by allogeneic stem cell transplantation in the case of adult patients.  As for most cancers, some patients respond well to the initial treatment and others less well.  The task of researchers developing more personalized treatment regimes is to find out how to identify how patients will respond before they start standardized therapy; this will avoid some patients having unpleasant treatments that have no effect for them and allow them to start a more effective one more easily.

Although patients with ALL may have similar symptoms, doctors and scientists know that when they look at the genomes of different patients they find many different errors where genetic material has been duplicated, deleted or moved around. Although all of us carry many of these “errors” or changes, it is not known how all of them affect our health, if they do at all. This is the case for the three genes in this study CDNKN2/ARF and CDNKN2B, many ALL patients have one or both copies of these genes deleted and Dr Genescà and her colleagues studied patients enrolled in the Spanish Programme for the Treatment of Malignant Hemopathies (PETHEMA) to find out how this affected the prognosis of their leukaemia.

55% of the patients studied had one or both of these genetic deletions. The researchers were able to show that these patients responded better to the initial treatment, with levels of leukaemia cells left in their blood afterwards below the levels at which they are considered to have the disease. This is an excellent initial result, although in many cases of ALL, malignant cells dormant in the body eventually come back to cause a relapse. Eulàlia Genescà told us, “Using this genetic information together with the patient’s response to the first treatment we would be able to identify which patients might not need a bone marrow transplant.”  She added, “Although it might seem strange, these genetic deletions are a sign of better outcomes in patients. We now need to carry out studies with a much larger group and to confirm these results.  I will be delighted if this test can be included in the standard protocol in the future.”

Original article

Frequency and clinical impact of CDKN2A/ARF/CDKN2B gene deletions as assessed by in-depth genetic analyses in adult T cell acute lymphoblastic leukemia

Genescà E, Lazarenkov A, Morgades M, Berbis G, Ruíz-Xivillé N, Gómez-Marzo P, Ribera J, Juncà J, González-Pérez A, Mercadal S, Guardia R, Artola MT, Moreno MJ, Martínez-López J, Zamora L, Barba P, Gil C, Tormo M, Cladera A, Novo A, Pratcorona M, Nomdedeu J, González-Campos J, Almeida M, Cervera J, Montesinos P, Batlle M, Vives S, Esteve J, Feliu E, Solé F, Orfao A, Ribera JM.

J Hematol Oncol. 2018 Jul 24;11(1):96. doi: 10.1186/s13045-018-0639-8.  PMID: 30041662


Funding Information

This project was supported by the Asociación Española Contra el Cáncer, AECC (project ref.: GC16173697BIGA), by CERCA Program/Generalitat de Catalunya, the Catalan Government: 2014-SGR225 (GRE), Obra Social “La Caixa” and by Celgene Spain. E. Genescà is the recipient of agrant from the Spanish Health Ministry (ISCIII, CA12/00468) and an unrestricted grant from Gilead.A. Gonzalez-Perez is supported by a Ramon y Cajal fellowship (RYC-2013-14554) of the Educational Ministry (Madrid, Spain). This work was also partially supported by FEDER funds from the ISCIII (PT13/0010/0026, CIBERONC (CB16/12/00284 and CB16/12/00400), Madrid, Spain).