Immunogenetics shows that not all MBL are equal: the larger the clone, the more similar to CLL.

Anna Vardi, Antonis Dagklis, Lydia Scarfò, Diane F Jelinek, Darren Newton, Fiona Bennett, Julia Almeida, Arancha Rodriguez-Caballero, Sallie Allgood, Mark Lanasa, Agostino Cortelezzi, Ester Orlandi, Silvio Veronese, Marco Montillo, Andy Rawstron, Tait Shanafelt, Alberto Orfao, Kostas Stamatopoulos, Paolo Ghia

Research output: Contribution to journalArticle

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Abstract

Chronic lymphocytic leukemia (CLL) -like monoclonal B-cell lymphocytosis (MBL) shares common immunophenotype and cytogenetic abnormalities with CLL, from which it is discriminated by a cutoff value of 5 × 10(9)/L circulating clonal B cells. However, the clonal size in MBL is extremely variable and allows discrimination of two distinct entities (high-count [HC] and low-count [LC]-MBL) based on a cutoff value of 0.5 × 10(9)/L clonal B cells. HC-MBL is associated with lymphocytosis and progresses to CLL requiring treatment at a rate of 1.1% per year, whereas LC-MBL is found in the general population only through high-sensitivity techniques and carries limited, if any, risk of progression. We performed an immunogenetic profiling of 333 cases with CLL-like MBL supplemented by detailed comparisons with CLL, focusing especially on CLL Rai stage 0 (CLL-0). LC- and HC-MBL had similar somatic hypermutation status, yet different IGHV gene repertoires and frequencies of B-cell receptor (BcR) stereotypy. In particular, stereotyped BcRs were infrequent in LC-MBL and were often not CLL specific. In contrast, HC-MBL exhibited clear immunogenetic similarities to CLL-0. These findings indicate that LC-MBL may not represent a true preleukemic condition, thus differing from HC-MBL/CLL-0 in which the identification of factors endowing malignant potential is strongly warranted.

Original languageEnglish (US)
Pages (from-to)4521-4528
Number of pages8
JournalBlood
Volume121
Issue number22
DOIs
StatePublished - May 30 2013

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Immunogenetics
Lymphocytosis
B-Cell Chronic Lymphocytic Leukemia
B-Lymphocytes
Clone Cells
Cells
Genes
Gene Frequency
Chromosome Aberrations

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Immunogenetics shows that not all MBL are equal : the larger the clone, the more similar to CLL. / Vardi, Anna; Dagklis, Antonis; Scarfò, Lydia; Jelinek, Diane F; Newton, Darren; Bennett, Fiona; Almeida, Julia; Rodriguez-Caballero, Arancha; Allgood, Sallie; Lanasa, Mark; Cortelezzi, Agostino; Orlandi, Ester; Veronese, Silvio; Montillo, Marco; Rawstron, Andy; Shanafelt, Tait; Orfao, Alberto; Stamatopoulos, Kostas; Ghia, Paolo.

In: Blood, Vol. 121, No. 22, 30.05.2013, p. 4521-4528.

Research output: Contribution to journalArticle

Vardi, A, Dagklis, A, Scarfò, L, Jelinek, DF, Newton, D, Bennett, F, Almeida, J, Rodriguez-Caballero, A, Allgood, S, Lanasa, M, Cortelezzi, A, Orlandi, E, Veronese, S, Montillo, M, Rawstron, A, Shanafelt, T, Orfao, A, Stamatopoulos, K & Ghia, P 2013, 'Immunogenetics shows that not all MBL are equal: the larger the clone, the more similar to CLL.', Blood, vol. 121, no. 22, pp. 4521-4528. https://doi.org/10.1182/blood-2012-12-471698
Vardi, Anna ; Dagklis, Antonis ; Scarfò, Lydia ; Jelinek, Diane F ; Newton, Darren ; Bennett, Fiona ; Almeida, Julia ; Rodriguez-Caballero, Arancha ; Allgood, Sallie ; Lanasa, Mark ; Cortelezzi, Agostino ; Orlandi, Ester ; Veronese, Silvio ; Montillo, Marco ; Rawstron, Andy ; Shanafelt, Tait ; Orfao, Alberto ; Stamatopoulos, Kostas ; Ghia, Paolo. / Immunogenetics shows that not all MBL are equal : the larger the clone, the more similar to CLL. In: Blood. 2013 ; Vol. 121, No. 22. pp. 4521-4528.
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AU - Scarfò, Lydia

AU - Jelinek, Diane F

AU - Newton, Darren

AU - Bennett, Fiona

AU - Almeida, Julia

AU - Rodriguez-Caballero, Arancha

AU - Allgood, Sallie

AU - Lanasa, Mark

AU - Cortelezzi, Agostino

AU - Orlandi, Ester

AU - Veronese, Silvio

AU - Montillo, Marco

AU - Rawstron, Andy

AU - Shanafelt, Tait

AU - Orfao, Alberto

AU - Stamatopoulos, Kostas

AU - Ghia, Paolo

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N2 - Chronic lymphocytic leukemia (CLL) -like monoclonal B-cell lymphocytosis (MBL) shares common immunophenotype and cytogenetic abnormalities with CLL, from which it is discriminated by a cutoff value of 5 × 10(9)/L circulating clonal B cells. However, the clonal size in MBL is extremely variable and allows discrimination of two distinct entities (high-count [HC] and low-count [LC]-MBL) based on a cutoff value of 0.5 × 10(9)/L clonal B cells. HC-MBL is associated with lymphocytosis and progresses to CLL requiring treatment at a rate of 1.1% per year, whereas LC-MBL is found in the general population only through high-sensitivity techniques and carries limited, if any, risk of progression. We performed an immunogenetic profiling of 333 cases with CLL-like MBL supplemented by detailed comparisons with CLL, focusing especially on CLL Rai stage 0 (CLL-0). LC- and HC-MBL had similar somatic hypermutation status, yet different IGHV gene repertoires and frequencies of B-cell receptor (BcR) stereotypy. In particular, stereotyped BcRs were infrequent in LC-MBL and were often not CLL specific. In contrast, HC-MBL exhibited clear immunogenetic similarities to CLL-0. These findings indicate that LC-MBL may not represent a true preleukemic condition, thus differing from HC-MBL/CLL-0 in which the identification of factors endowing malignant potential is strongly warranted.

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