State of the art laboratories

Research in to the basic, epidemiological, preventive, clinical and translational aspects of leukemia and other hematologic malignancies

A New Partnership of Public, Private and Competitive Funding

Patients, Scientists, Doctors; working together to cure leukemia

Research centred on patients

Caring research


Recent publications

Costa D, Muñoz C, Carrió A, Arias A, Gómez C, Solé F, Espinet B, Azaceta G, Calasanz MJ, Nomdedeu M, Calvo X, Campo E, Nomdedeu B

Refining the Breakpoints of Three New Translocations Identified in Myelodysplastic Syndromes.

Acta Haematol. 2016, 135 (2) 94-100. Epub 28 Oct 2015
Recurrent translocations are uncommon in myelodysplastic syndromes (MDS). Three new recurrent translocations, namely der(12)t(3;12)(q13;p13), t(11;13;22)(q13;q14;q12) and der(17)t(13;17)(q21;p13), identified by conventional cytogenetics (CC) in 4 MDS patients, were further characterized using a panel of commercial and homemade fluorescence in situ hybridization (FISH) probes. The goal of this study was to determine the precise breakpoints and to identify genes that could be related with the neoplastic process. Half of the breakpoints (4/8) were precisely identified and in the remaining half they were narrowed to a region ranging from 14 to 926 kb. All the studied breakpoints had interstitial or terminal deletions ranging from 536 kb to 89 Mb, and only those 7 Mb were detected by CC. The genes located in or around the breakpoints described in our study have not been previously related to MDS. The deleted regions include the ETV6 and RB1 genes, among others, and exclude the TP53 gene. FISH studies were useful to refine the breakpoints of the translocations, but further studies are needed to determine the role of the involved genes in the neoplastic process.
More information
Braulke F, Müller-Thomas C, Götze K, Platzbecker U, Germing U, Hofmann WK, Giagounidis AA, Lübbert M, Greenberg PL, Bennett JM, Solé F, Slovak ML, Ohyashiki K, Le Beau MM, Tüchler H, Pfeilstöcker M, Hildebrandt B, Aul C, Stauder R, Valent P, Fonatsch C, Bacher U, Trümper L, Haase D, Schanz J

Frequency of del(12p) is commonly underestimated in myelodysplastic syndromes: Results from a German diagnostic study in comparison with an international control group.

Genes Chromosomes Cancer Dec 2015, 54 (12) 809-17. Epub 10 Sep 2015
In myelodysplastic syndromes (MDS), deletion of the short arm of chromosome 12 (del(12p)) is usually a small abnormality, rarely detected as a single aberration by chromosome banding analysis (CBA) of bone marrow metaphases. Del(12p) has been described in 0.6 to 5% of MDS patients at initial diagnosis and is associated with a good to intermediate prognosis as a sole anomaly according to current scoring systems. Here, we present the results of a systematic del(12p) testing in a German prospective diagnostic study ( NCT01355913) on 367 MDS patients in whom CD34+ peripheral blood cells were analysed for the presence of del(12p) by sequential fluorescence in situ hybridization (FISH) analyses. A cohort of 2,902 previously published MDS patients diagnosed by CBA served as control. We demonstrate that, using a sensitive FISH technique, 12p deletion occurs significantly more frequently in MDS than previously described (7.6% by CD34+ PB-FISH vs. 1.6% by CBA, P < 0.001) and is often associated with other aberrations (93% by CD34+ PB-FISH vs. 60% by CBA). Additionally, the detection rate can be increased by repeated analyses in a patient over time which is important for the patient´s prognosis to distinguish a sole anomaly from double or complex aberrations. To our knowledge, this is the first study to screen for 12p deletions with a suitable probe for ETV6/TEL in 12p13. Our data suggest that the supplement of a probe for the detection of a 12p deletion to common FISH probe panels helps to avoid missing a del(12p), especially as part of more complex aberrations. © 2015 Wiley Periodicals, Inc.
More information
Ribera J, Morgades M, Zamora L, Montesinos P, Gómez-Seguí I, Pratcorona M, Sarrà J, Guàrdia R, Nomdedeu J, Tormo M, Martínez-Lopez J, Hernández-Rivas JM, González-Campos J, Barba P, Escoda L, Genescà E, Solé F, Millá F, Feliu E, Ribera JM

Prognostic significance of copy number alterations in adolescent and adult patients with precursor B acute lymphoblastic leukemia enrolled in PETHEMA protocols.

Cancer 1 Nov 2015, 121 (21) 3809-17. Epub 20 Jul 2015
Some copy number alterations (CNAs) have independent prognostic significance for adults with acute lymphoblastic leukemia (ALL).
More information
Palomo L, Xicoy B, Garcia O, Mallo M, Ademà V, Cabezón M, Arnan M, Pomares H, Larrayoz MJ, Calasanz MJ, Maciejewski JP, Huang D, Shih LY, Ogawa S, Cervera J, Such E, Coll R, Grau J, Solé F, Zamora L

Impact of SNP array karyotyping on the diagnosis and the outcome of chronic myelomonocytic leukemia with low risk cytogenetic features or no metaphases.

Am. J. Hematol. 28 Oct 2015, . Epub 28 Oct 2015
Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic disorder with heterogeneous clinical, morphological and genetic characteristics. Clonal cytogenetic abnormalities are found in 20-30% of patients with CMML. Patients with low risk cytogenetic features (normal karyotype and isolated loss of Y chromosome) account for approximately 80% of CMML patients and often fall into the low risk categories of CMML prognostic scores. We hypothesized that single nucleotide polymorphism arrays (SNP-A) karyotyping could detect cryptic chromosomal alterations with prognostic impact in these subgroup of patients. SNP-A were performed in 128 CMML patients at diagnosis with low risk karyotypes or uninformative results for conventional G-banding cytogenetics (CC). Copy number alterations (CNAs) and regions of copy number neutral loss of heterozygosity (CNN-LOH) were detected in 67% of patients. Recurrent CNAs included gains in regions 8p12 and 21q22 as well as losses in 10q21.1 and 12p13.2. Interstitial CNN-LOHs were recurrently detected in the following regions: 4q24-4q35, 7q32.1-7q36.3 and 11q13.3-11q25. Statistical analysis showed that some of the alterations detected by SNP-A associated with the patients' outcome. A shortened overall survival (OS) and progression free survival (PFS) was observed in cases where the affected size of the genome (considering CNAs and CNN-LOHs) was >11 Mb. In addition, presence of interstitial CNN-LOH was predictive of poor OS. Presence of CNAs associated with poorer OS and PFS in the patients with myeloproliferative CMML. Overall, SNP-A analysis increased the diagnostic yield in patients with low risk cytogenetic features or uninformative CC and added prognostic value to this subset of patients. This article is protected by copyright. All rights reserved.
More information
McGraw KL, Cluzeau T, Sallman DA, Basiorka AA, Irvine BA, Zhang L, Epling-Burnette PK, Rollison DE, Mallo M, Sokol L, Solé F, Maciejewski J, List AF

TP53 and MDM2 single nucleotide polymorphisms influence survival in non-del(5q) myelodysplastic syndromes.

Oncotarget 27 Oct 2015, 6 (33) 34437-45. Epub 25 Sep 2015
P53 is a key regulator of many cellular processes and is negatively regulated by the human homolog of murine double minute-2 (MDM2) E3 ubiquitin ligase. Single nucleotide polymorphisms (SNPs) of either gene alone, and in combination, are linked to cancer susceptibility, disease progression, and therapy response. We analyzed the interaction of TP53 R72P and MDM2 SNP309 SNPs in relationship to outcome in patients with myelodysplastic syndromes (MDS). Sanger sequencing was performed on DNA isolated from 208 MDS cases. Utilizing a novel functional SNP scoring system ranging from +2 to -2 based on predicted p53 activity, we found statistically significant differences in overall survival (OS) (p = 0.02) and progression-free survival (PFS) (p = 0.02) in non-del(5q) MDS patients with low functional scores. In univariate analysis, only IPSS and the functional SNP score predicted OS and PFS in non-del(5q) patients. In multivariate analysis, the functional SNP score was independent of IPSS for OS and PFS. These data underscore the importance of TP53 R72P and MDM2 SNP309 SNPs in MDS, and provide a novel scoring system independent of IPSS that is predictive for disease outcome.
More information