Birgitte Roland

Influence of cytogenetics in patients with relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone: adverse effect of deletion 17p13

Although the combination of lenalidomide and dexamethasone is effective therapy for patients with relapsed/refractory multiple myeloma, the influence of high-risk cytogenetic abnormalities on outcomes is unknown. This subanalysis of a large, open-label study investigated the effects of the most common unfavorable cytogenetic abnormalities detected by fluorescence in situ hybridization, del(13q), t(4;14), and del(17p13), in 130 evaluable patients treated with this regimen. Whereas patients with either del(13q) or t(4;14) experienced a median time to progression and overall survival comparable with those without these cytogenetic abnormalities, patients with del(17p13) had a significantly worse outcome, with a median time to progression of 2.22 months (hazard ratio, 2.82; P < .001) and median overall survival of 4.67 months (hazard ratio, 3.23; P < .001). Improved therapeutic strategies are required for this subgroup of patients. This study was registered at www.ClinicalTrials.gov as #NCT00179647.

Familial complex chromosomal rearrangement resulting in duplication/deletion of 6q1c to 6q16

A familial complex chromosomal rearrangement (CCR) was ascertained through a mentally retarded, dysmorphic individual. Carriers of the CCR have the karyotype 46,XX or XY, t(6;15)(q16;q21), ins(3;6)(q12;q14q16), and malsegregation of the CCR resulted in loss of the segment 6q14 to 6q16 in the proband, and in an additional copy of the same segment in three members of the extended family. The proband has features similar to other reported cases with deletion of 6q1. The individuals with duplication of 6q14 to 6q16 have moderate mental retardation, short stature, obesity, microcephaly, brachycephaly, a short smooth philtrum, central hair whorl, simian creases, 5th finger brachydactyly and skeletal disproportion. In the 4‐generation family, CCR carriers have a 20% empiric risk of phenotypically abnormal livebirths.

Trisomy 21 and isodicentric chromosome 21 in Kostmann syndrome following treatment with G-CSF

A child with Kostmann syndrome, or severe congenital neutropenia, developed myelodysplastic syndrome after 6 years of treatment with rhG-CSF. The bone marrow karyotype showed acquired trisomy 21, and in some cells pentasomy 21 due to two isodicentric chromosomes 21. This is the second report of a patient with Kostmann syndrome and acquired trisomy 21.

Transient myelodysplastic syndrome associated with isochromosome 7q abnormality.

Myelodysplastic syndrome (MDS) in childhood is a rare hematological condition that is often associated with cytogenetic abnormalities, the most common being monosomy 7/del(7q). The clinical course of MDS can vary from stable disease to rapid progression into acute leukemia. Rarely, spontaneous remission of MDS has been observed. The authors report the first case of a transient MDS associated with a clonal marrow cytogenetic abnormality consisting of isochromosome 7q in a previously well child. Without intervention, the bone marrow cytogenetics reverted to normal and there was complete hematologic recovery. This case illustrates the importance of close follow-up in a child presenting with MDS, to detect spontaneous recovery or evolution of the disease.

A case of down syndrome with acute lymphoblastic leukemia and isochromosome Xp

A 3-year, 9-month-old girl with trisomy 21 was diagnosed with acute lymphoblastic leukemia (ALL). The karyotype of her leukemic cells at diagnosis-48,XX,+i(X)(p10),+21c-included an extra, structurally abnormal X chromosome as the sole acquired abnormality. While an extra X chromosome is a common abnormality in childhood ALL, it is seldom the only acquired aberration. Furthermore, an additional X chromosome that is structurally abnormal is rare, and has not been reported previously as a solitary abnormality. Here we report a novel karyotype in childhood ALL and review the eight previously described cases of ALL with an extra X isochromosome as the only acquired abnormality.

Hyperdiploid karyotype in a choroid plexus papilloma

A choroid plexus papilloma from a 23-month-old child was found to have a hyperdiploid karyotype. This karyotype is compared with that of other choroid plexus papillomas. Our results are also compared with flow cytometry results and the karyotypes of choroid plexus carcinomas.

Evidence of chromosome 9 origin of the euchromatic variant band within 9qh

Hoo JJ, Szego K, Wong P, Roland B. Evidence of chromosome 9 origin of the euchromatic variant band within 9qh.

A Case of Near-Triploidy in Chronic Myelogenous Leukemia

A 61-year-old woman with chronic myelogenous leukemia (CML) in accelerated phase had a near-triploid bone-marrow karyotype. This karyotype is an unusual finding in CML, as we review 12 previously published similar cases. These patients do not differ clinically from other patients with CML in blast crisis. The cytogenetic features of near-diploid and near-triploid CML are similar, except that relative loss of chromosomes is more common and that isochromosome 17q has not been reported in near-triploid CML.

An interstitial deletion of the long arm of chromosome 13

A case of an interstitial deletion of chromosome 13, identified as 46,XY,del(13)(q22q31), is reported in a child with psychomotor retardation, prominent low‐set ears, epicanthus, hypertelorism, broad nasal bridge, hypoplastic fifth fingers and abnormal dermatoglyphics. This patient is compared to others in the literature with a similar deletion.

Isoderivative chromosome 20 in bone marrow: three new cases

Deletion of the long arm of chromosome 20, or 20q , is one of the most common chromosome rearrangements in myeloid neoplasia and is commonly observed as the sole abnormality. It is associated with a favorable prognosis in myelodysplastic syndrome (MDS) [1], and with an intermediate prognosis in acute myeloid leukemia (AML) [2]. Since 2004, several reports have described an isochromosome that is likely derived from a deleted chromosome 20dthat is, ider(20) [3e9]. Recently the ider(20) has been demonstrated to be isodicentric, with a breakpoint in proximal 20p in addition to those in 20q [7,9]. Some authors have suggested that the clinical significance of ider(20), which has been reported in MDS and AML, differs from that of deletion 20q [3,7]. We have identified three cases of isoderivative chromosome 20, which further characterize the range of pathologic and clinical phenotype associated with this entity. The cytogenetic karyotyping and fluorescence in situ hybridization (FISH) results using probes for the 20q telomere are illustrated in Figure 1. The first patient was a 64-year-old man who presented with anemia and neutropenia. A bone marrow biopsy showed decreased myelopoiesis with normal morphology. Cytogenetic and FISH analysis revealed the karyotype as 46,XY,ider(20)del(20)(q11.2q13.3)[7].