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CD34+ cell of origin for immunoglobulin heavy chain variable region unmutated, but not mutated, chronic lymphocytic leukemia.
Perkins, Brandy; Showel, Margaret; Schoch, Laura; Imus, Philip H; Karantanos, Theodoros; Yonescu, Raluca; Morsberger, Laura; Ghiaur, Gabriel; Gladstone, Douglas E; Jones, Richard J.
Affiliation
  • Perkins B; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, John Hopkins University, Baltimore, MD, USA.
  • Showel M; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, John Hopkins University, Baltimore, MD, USA.
  • Schoch L; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, John Hopkins University, Baltimore, MD, USA.
  • Imus PH; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, John Hopkins University, Baltimore, MD, USA.
  • Karantanos T; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, John Hopkins University, Baltimore, MD, USA.
  • Yonescu R; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, John Hopkins University, Baltimore, MD, USA.
  • Morsberger L; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, John Hopkins University, Baltimore, MD, USA.
  • Ghiaur G; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, John Hopkins University, Baltimore, MD, USA.
  • Gladstone DE; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, John Hopkins University, Baltimore, MD, USA.
  • Jones RJ; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, John Hopkins University, Baltimore, MD, USA.
Leuk Lymphoma ; 63(7): 1617-1623, 2022 07.
Article in En | MEDLINE | ID: mdl-35343368
ABSTRACT
The clinical course of chronic lymphocytic leukemia (CLL) is highly variable. Immunoglobulin heavy chain variable region (IgHV) mutation status is among the most important prognostic factors, with unmutated IgHV associated with inferior outcomes. CLL presumably arises from mature B cells. However, we hypothesized that IgHV unmutated CLL could arise early in B cell differentiation. We prospectively studied 29 patients with mutated and 88 with unmutated IgHV CLL for the presence of CD34+CD19+ cells harboring CLL chromosomal abnormalities. CD34+CD19+ cells were never detected in mutated CLL. In contrast, a small but distinct population of CD34+CD19+ cells harboring the CLL chromosomal abnormality was present in 86/88 patients with unmutated IgHV across all cytogenetic subtypes. Moreover, the CD34+CD19+ cells generated a 3.8 ± 0.7 fold CLL cell expansion over 3-4 weeks in cultures containing IL-3 and IL-2. Unmutated IgHV CLL appears to arise in CD34+ B cells, which perhaps contributes to its poorer prognosis.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Leukemia, Lymphocytic, Chronic, B-Cell / Immunoglobulin Heavy Chains / Precursor Cells, B-Lymphoid / Mutation Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Leuk Lymphoma Journal subject: HEMATOLOGIA / NEOPLASIAS Year: 2022 Document type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Leukemia, Lymphocytic, Chronic, B-Cell / Immunoglobulin Heavy Chains / Precursor Cells, B-Lymphoid / Mutation Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Leuk Lymphoma Journal subject: HEMATOLOGIA / NEOPLASIAS Year: 2022 Document type: Article Affiliation country: United States