Chronic lymphocytic leukemia patients with a V1-69 gene rearrangement do not have inferior survival with respect to patients that express other unmutated VH genes

Panovska-Stavridis, Irina; Ivanovski, Martin; Siljanovski, Nikola; Čevreska, Lidija; Efremov, Dimitar G.

doi:10.1016/j.leukres.2006.05.008

Cited by 13 publications

(15 citation statements)

References 8 publications

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“…The presence of certain subgenes is associated with a patient's adverse prognosis, as previously described in the analyzed IGHV3-21 and IGHV1-69 subgenes [10][11][12]26]. In the aforementioned group, the IGHV1-69 and IGHV3-21 subgenes were present in 51 (12.2%) and 29 (7%) patients, respectively.…”

Section: Discussionsupporting

confidence: 60%

“…Two-thirds of IGHV3-21 patients have M IGHV status, with a relatively low percentage of mutations; on the other side, patients with IGHV1-69 mostly have UM IGHV status [10,11,26]. In the present group, M IGHV status was found in 55% of IGHV3-21 patients, with a mean number of mutations reaching 3.58%.…”

Section: Discussionmentioning

confidence: 39%

“…Selected V gene segments have prognostic value in CLL. These include IGHV3-21 and IGHV1-69 [5,10,11]. The presence of IGHV3-21 in CLL is associated with poor prognosis regardless of its mutation status.…”

mentioning

confidence: 99%

“…Patients with this subgene appear to be a homogeneous group, with more frequent advanced clinical stage of the disease requiring early therapeutic intervention. However, their survival is not worse than that of other patients with UM IGHV [11]. It was found that IGHV1-69 is expressed by 30% of unmutated CLL and rearranges to a restricted number of IGHD and IGHJ genes, often generating long and rather similar HCDR3 regions [18].…”

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confidence: 99%

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Biological and clinical characteristics of patients with chronic lymphocytic leukemia with the IGHV3-21 and IGHV1-69; analysis of data from a single center

Urbanová¹,

Humplikova²,

Drimalova³

et al. 2015

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This study aimed at mapping the frequency of IGHV3-21 and IGHV1-69 in a group of 417 patients newly diagnosed with chronic lymphocytic leukemia (CLL) and described basic characteristics, cytogenetic abnormalities and prognosis of these patient subgroups. IGHV3-21 was found in 29 patients (7%) and IGHV1-69 in 51 patients (12.4%). The median overall survival (OS) rates were 97 months and 85 months in the IGHV3-21 and IGHV1-69 groups, respectively. In this small group of patients, the study failed to show a difference in OS of IGHV3-21 patients with mutated and unmutated IGHV status (p<0.597). There was also no difference in OS between IGHV3-21 patients with mutated IGHV status and all patients in the group having unmutated IGHV status (p<0.245). On the other hand, patients with IGHV3-21 and the presence of some other adverse prognostic factors (age ≥ 65 years, lymphocyte count ≥ 50×109/L, serum thymidine kinase ≥ 9U/L, deletion of 17p) had statistically significantly worse OS than IGHV3-21 patients without the presence of these prognostic factors. The multivariate analysis of an entire group of Binet clinical stage A patients proved that the presence of IGHV3-21 is as an independent adverse prognostic factor even though there was no statistical difference in OS between patients with IGHV3-21 and those without IGHV3-21 in the entire group (p<0.769). Patients with IGHV1-69 had the same probablility of OS irrespective of the presence of other adverse prognostic factors; their OS was significantly shorter as compared with the other patients from the entire group (p<0.03).The study mapped the occurrence of recurrent cytogenetic changes detected by FISH in IGHV3-21 (subset #2 and non-subset #2) and IGHV1-69 and compared it with the occurrence of recurrent changes in the entire group of patients. In IGHV1-69 and in subset #2 IGHV3-21, higher proportions of deletion of 11q were found (30% and 31%, respectively), with the deletion being present in 19.2% of the entire group of patients. None of the 3 patients with IGHV3-21 and deletion of 17p had subset #2. Patients with subset #2 IGHV3-21 had higher proportions of deletion of 13 (69%) as compared with non-subset #2 IGHV3-21 patients (27%).

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 39%

mentioning

confidence: 99%

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confidence: 99%

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Biological and clinical characteristics of patients with chronic lymphocytic leukemia with the IGHV3-21 and IGHV1-69; analysis of data from a single center

Urbanová¹,

Humplikova²,

Drimalova³

et al. 2015

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“…Although IgHV1-69 gene expression is associated with an unfavourable clinical course [1,21,25,26], mutated IgHV1-69 cases have been described [20 -22], and it has been suggested that the survival of patients with unmutated IgHV1-69 gene rearrangements does not differ significantly from patients with alternative unmutated IgHV gene usage [25]. Furthermore, several stereotyped IgHV1-69 subsets have recently been described [20,21].…”

Section: Introductionmentioning

confidence: 99%

Mutated IgHV1-69 gene usage represents a distinct subgroup associated with indolent disease in chronic lymphocytic leukemia

Galligan

Catherwood

Matthews

et al. 2008

Leukemia & Lymphoma

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Biased IgHV gene usage in chronic lymphocytic leukemia (CLL) is well documented and suggests antigen involvement in leukemogenesis. IgHV1-69 is one of the most frequently rearranged IgHV genes in CLL and the majority of IgHV1-69 cases lack somatic hypermutation and display poor prognosis. However, its independent prognostic impact remains uncertain given reports showing a low proportion of mutated IgHV1-69 cases and stereotyped IgHV1-69 subsets with divergent clinical outcome. We assessed the frequency and clinical significance of IgHV1-69 gene usage in a cohort of 330 CLL patients. Functional IgHV1-69 gene rearrangements were detected in 32 cases (9.7%), 31 of which were characterised further. Seven (22.6%) were found to have undergone somatic hypermutation. This subgroup had shorter and more diverse complementarity determining region 3 (CDR3) sequences compared with unmutated IgHV1-69 cases. In addition, mutated IgHV1-69 gene status was associated with lower cell surface CD38 expression and less progressive disease as monitored by Binet staging, lymphocyte doubling time and requirement of chemotherapeutic intervention. To conclude, we present data confirming that IgHV1-69 gene rearrangements in CLL are not exclusively associated with unmutated IgHV status. In addition, we show that a somatically hypermutated subgroup may demonstrate more indolent characteristics despite the general association of IgHV1-69 gene usage with aggressive disease.

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Current Awareness in Hematological Oncology

2007

Hematological Oncology

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In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of hematological oncology. Each bibliography is divided into 14 sections: 1 Reviews; 2 General; Leukemias: 3 Lymphoblastic; 4 Myeloid & Myelodysplastic Syndromes; 5 Chronic; 6 Others; Lymphomas: 7 Hodgkin's; 8 Non‐Hodgkin's; 9 Plasmacytomas/Multiple Myelomas; 10 Others; 11 Bone Marrow Transplantation; 12 Cytokines; 13 Diagnosis; 14 Cytogenetics. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted.

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Chronic lymphocytic leukemia patients with a V1-69 gene rearrangement do not have inferior survival with respect to patients that express other unmutated VH genes

Cited by 13 publications

References 8 publications

Biological and clinical characteristics of patients with chronic lymphocytic leukemia with the IGHV3-21 and IGHV1-69; analysis of data from a single center

Biological and clinical characteristics of patients with chronic lymphocytic leukemia with the IGHV3-21 and IGHV1-69; analysis of data from a single center

Mutated IgHV1-69 gene usage represents a distinct subgroup associated with indolent disease in chronic lymphocytic leukemia

Current Awareness in Hematological Oncology

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