Cytogenetic and molecular predictors of response in patients with myeloid malignancies without del[5q] treated with lenalidomide

• Published in: Journal of hematology and oncology Vol. 5; no. 1; p. 4
• Main Authors: Sugimoto, Yuka, Sekeres, Mikkael A, Makishima, Hideki, Traina, Fabiola, Visconte, Valeria, Jankowska, Anna, Jerez, Andres, Szpurka, Hadrian, O'Keefe, Christine L, Guinta, Kathryn, Afable, Manuel, Tiu, Ramon, McGraw, Kathy L, List, Alan F, Maciejewski, Jaroslaw
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 05.03.2012; BioMed Central; BMC
• Subjects: Aged; Aged, 80 and over; Blood; Bone marrow; Cancer; Cell division; Chromosome Aberrations; Chromosome Deletion; Chromosomes; Chromosomes, Human, Pair 5 - genetics; del[5q]; Drug therapy; Female; Fluorescence in situ hybridization; Genetic aspects; Hematology; Humans; In Situ Hybridization, Fluorescence; Karyotyping; Lenalidomide; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - pathology; Male; Metaphase cytogenetics; Middle Aged; Mutation; Mutation - genetics; Myelodysplastic syndromes; Myelodysplastic Syndromes - drug therapy; Myelodysplastic Syndromes - genetics; Myelodysplastic Syndromes - pathology; Myeloproliferative Disorders - drug therapy; Myeloproliferative Disorders - genetics; Myeloproliferative Disorders - pathology; Oncology; Polymorphism, Single Nucleotide - genetics; Prognosis; Single nucleotide polymorphism array; Thalidomide - analogs & derivatives; Thalidomide - therapeutic use
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/1756-8722-5-4

While lenalidomide (LEN) shows high efficacy in myelodysplastic syndromes (MDS) with del[5q], responses can be also seen in patients presenting without del[5q]. We hypothesized that improved detection of chromosomal abnormalities with new karyotyping tools may better predict response to LEN. We have studied clinical, molecular and cytogenetic features of 42 patients with MDS, myeloproliferative neoplasms (MPN), MDS/MPN overlap syndromes and secondary acute myeloid leukemia (sAML) without del[5q] by metaphase cytogenetics (MC) who underwent therapy with LEN. Fluorescence in situ hybridization (FISH) or single nucleotide polymorphism array (SNP-A)-based karyotyping marginally increased the diagnostic yield over MC, detecting 2/42 (4.8%) additional cases with del[5q], one of whom were responded to LEN. Responses were more often observed in patients with a normal karyotype by MC (60% vs abnormal MC; 17%, p = .08) and those with gain of chromosome 8 material by either of all 3 karyotyping methods (83% vs all other chromosomal abnormalities; 44% p = .11). However, 5 out of those 6 patients received combined LEN/AZA therapy and it may also suggest those with gain of chromosome 8 material respond well to AZA. The addition of FISH or SNP-A did not improve the predictive value of normal cytogenetics by MC. Mutational analysis of TET2, UTX, CBL, EZH2, ASXL1, TP53, RAS, IDH1/2, and DNMT-3A was performed on 21 of 41 patients, and revealed 13 mutations in 11 patients, but did not show any molecular markers of responsiveness to LEN. Normal karyotype and gain of chromosome 8 material was predictive of response to LEN in non-del[5q] patients with myeloid malignancies.