PreB1 (CD10-) acute lymphoblastic leukemia: Immunophenotypic and genomic characteristics, clinical features and outcome in 38 adults and 26 children

B. Lenormand; M. C. Béné; J. F. Lesesve; C. Bastard; H. Tilly; M. P. Lefranc; G. C. Faure; R. Garand; A. Falkenrodt; G. Kandel; E. Solary; M. Maynadié; M. P. Callat; F. Thouret; M. Monconduit; J. P. Vannier

doi:10.3109/10428199809092688

PreB1 (CD10^-) acute lymphoblastic leukemia: Immunophenotypic and genomic characteristics, clinical features and outcome in 38 adults and 26 children

B. Lenormand, M. C. Béné, J. F. Lesesve, C. Bastard, H. Tilly, M. P. Lefranc, G. C. Faure, R. Garand, A. Falkenrodt, G. Kandel, E. Solary, M. Maynadié, M. P. Callat, F. Thouret, M. Monconduit, J. P. Vannier

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

Abstract

The less differentiated stage (CD10-) of B-lineage acute lymphoblastic leukaemia (ALL) described as preB1-ALL in the GEIL nomenclature, accounts for less than 10% of ALL. It is classically considered to be associated with translocation (4;11)(q21;q23), and to have a poor prognosis. We report an extensive immunophenotypic, genomic and clinical study of a series of 64 preB-1 ALL patients, representing 6.3% of a cohort of consecutive ALLs. The engagement of preB 1-ALL cells in the B-lineage was confirmed by their B-lineage score, equal to or higher than 2. In addition, more than 90% of the cases tested showed rearranged IGH genes. Translocation (4;11) was the most frequent karyotypic anomaly seen, but only accounted for 24% of the preB1-ALL cases tested. Expression of the myeloid associated antigen CD15 was also found with high incidence in this subset. Clinical and biological features at presentation showed more significant differences between preB1- and T-ALL than between preB1- and preB2-ALL (CD10⁺). However, outcome characteristics of the 22 children with preB1-ALL confirmed the worse prognosis of this entity.

Original language	English
Pages (from-to)	329-342
Number of pages	14
Journal	Leukemia and Lymphoma
Volume	28
Issue number	3-4
DOIs	https://doi.org/10.3109/10428199809092688
Publication status	Published - 1 Jan 1998
Externally published	Yes

Keywords

Acute
Antigens
Blotting
CD10
Genes
Immunoglobulin
Leukemia
Lymphocytic
Receptor
Southern
T-cell

Access to Document

10.3109/10428199809092688

Cite this

Lenormand, B., Béné, M. C., Lesesve, J. F., Bastard, C., Tilly, H., Lefranc, M. P., Faure, G. C., Garand, R., Falkenrodt, A., Kandel, G., Solary, E., Maynadié, M., Callat, M. P., Thouret, F., Monconduit, M., & Vannier, J. P. (1998). PreB1 (CD10^-) acute lymphoblastic leukemia: Immunophenotypic and genomic characteristics, clinical features and outcome in 38 adults and 26 children. Leukemia and Lymphoma, 28(3-4), 329-342. https://doi.org/10.3109/10428199809092688

@article{3d91aa93cf9d45a3b4b782fc836bcd03,

title = "PreB1 (CD10-) acute lymphoblastic leukemia: Immunophenotypic and genomic characteristics, clinical features and outcome in 38 adults and 26 children",

abstract = "The less differentiated stage (CD10-) of B-lineage acute lymphoblastic leukaemia (ALL) described as preB1-ALL in the GEIL nomenclature, accounts for less than 10% of ALL. It is classically considered to be associated with translocation (4;11)(q21;q23), and to have a poor prognosis. We report an extensive immunophenotypic, genomic and clinical study of a series of 64 preB-1 ALL patients, representing 6.3% of a cohort of consecutive ALLs. The engagement of preB 1-ALL cells in the B-lineage was confirmed by their B-lineage score, equal to or higher than 2. In addition, more than 90% of the cases tested showed rearranged IGH genes. Translocation (4;11) was the most frequent karyotypic anomaly seen, but only accounted for 24% of the preB1-ALL cases tested. Expression of the myeloid associated antigen CD15 was also found with high incidence in this subset. Clinical and biological features at presentation showed more significant differences between preB1- and T-ALL than between preB1- and preB2-ALL (CD10+). However, outcome characteristics of the 22 children with preB1-ALL confirmed the worse prognosis of this entity.",

keywords = "Acute, Antigens, Blotting, CD10, Genes, Immunoglobulin, Leukemia, Lymphocytic, Receptor, Southern, T-cell",

author = "B. Lenormand and B{\'e}n{\'e}, {M. C.} and Lesesve, {J. F.} and C. Bastard and H. Tilly and Lefranc, {M. P.} and Faure, {G. C.} and R. Garand and A. Falkenrodt and G. Kandel and E. Solary and M. Maynadi{\'e} and Callat, {M. P.} and F. Thouret and M. Monconduit and Vannier, {J. P.}",

note = "Funding Information: Engagement of preB 1 -ALL cells in the B-lineage growth factors. The SEM cell line indeed is responsive has been debated because CD19 can also be expressed to IL-7,[391and it has also been shown that reduced on myeloid We took great care to assess the CDlO/NEP enzymatic activity may facilitate the presence of other B-lineage markers, and reach a score development of small-cell carcinomas of the lung.{\textquoteleft}@] of 2 for that lineage. In the entire series of ALL tested, The high incidence of rearrangement of both IGH we found no case with an isolated expression of CD19 genes, not rarely associated with TCR genes and no other B-marker (data not shown). As in previ-rearrangements could also indicate anomalies in such ous studies[{\textquoteright}0*{\textquoteright}{\textquoteright}a]n d in our own, genotypic analyses regulatory factors as the recombination activating also concur with the fact that these cells are engaged in gene-1 (RAG-1),[45i1n these cells. These concomitent B-cell differentiation, as more than 90% of the cases and conflicting rearrangements could be responsible tested showed rearranged IGH locus, frequently on for the arrest of cell differentiation. both chromosomes 14, while IGL loci were seldom In conclusion, the immunophenotypic subgroup of rearranged. However, more than one third of the cells preB 1-ALL appears to be larger than that merely iden-tested also had either TCRG or TCRB rearrangements tified by chromosome 1 1 alteration^,['*^^.^^] and stands although rarely both. A similar coindicence of IGH out as important to be identified properly through and TCR gene rearrangements has been reported in the immunophenotyping procedures. Presentation fea-SEM cell line.[391 tures may resemble those of other preB ALL, but this These immunophenotypic and genotypic character-series confirms the worse prognosis of this entity, istics nevertheless clearly assign preB 1-ALL to the especially in children. B-lineage, and our series indicates that this immuno- phenotype is not specifically restricted to any particu- lar age-range, as other studies had s ~ g g e s t e d . [ ~ * ~{\~A}c*k{\~n}o*w~le dgements We therefore investigated how these cells compared with preB2-ALL cells, which represent the common- est ALL immunophenotype, and also with the less fre- quent T-ALLs. Clinical and biological features at presentation confirmed the relationship between preB 1- ALL and B-lineage ALL, since more numerous differences were found between preB 1- and T-ALL than between preB1-and preB2-ALL. In an earlier series without infants,[38n1 o difference was observed in treatment outcome between 10 CD10-and 254 CD10+ B-lineage ALL cases. In our series, outcome characteristics of the 22 children and 38 adults with preB1 ALL, differed from those of preB2-ALL patients, and we were able to demonstrated the worse prognosis of this disease, more similar to that of T-ALL, especially in children. Cell growth and leukemogenesis in preB 1-ALL could be related to the absence of CDlO expression. CDlOheutral endopeptidase 24.1 I (CD 10NPE) has been reported as an important regulatory molecule, able to inactivate growth factors, or activate growth inhibitory pep tide^.[^^-^' Since preB 1- ALL cells lack this molecule, they could be more responsive to cell We wish to thank Dr T.H. Rabbitts for his kind gift of gene probes, and C. Canipel and P. Marie for their excellent technical assistance. This work was supported by a grant from the Association pour la Recherche sur le Cancer and from the Ligue Nationale Frangaise contre le Cancer (DCpartement de 1{\textquoteright}Eure et de la Seine-Maritime). The GEIL is “rCseau INSERM”.",

year = "1998",

month = jan,

day = "1",

doi = "10.3109/10428199809092688",

language = "English",

volume = "28",

pages = "329--342",

journal = "Leukemia and Lymphoma",

issn = "1042-8194",

number = "3-4",

}

Lenormand, B, Béné, MC, Lesesve, JF, Bastard, C, Tilly, H, Lefranc, MP, Faure, GC, Garand, R, Falkenrodt, A, Kandel, G, Solary, E, Maynadié, M, Callat, MP, Thouret, F, Monconduit, M & Vannier, JP 1998, 'PreB1 (CD10^-) acute lymphoblastic leukemia: Immunophenotypic and genomic characteristics, clinical features and outcome in 38 adults and 26 children', Leukemia and Lymphoma, vol. 28, no. 3-4, pp. 329-342. https://doi.org/10.3109/10428199809092688

TY - JOUR

T1 - PreB1 (CD10-) acute lymphoblastic leukemia

T2 - Immunophenotypic and genomic characteristics, clinical features and outcome in 38 adults and 26 children

AU - Lenormand, B.

AU - Béné, M. C.

AU - Lesesve, J. F.

AU - Bastard, C.

AU - Tilly, H.

AU - Lefranc, M. P.

AU - Faure, G. C.

AU - Garand, R.

AU - Falkenrodt, A.

AU - Kandel, G.

AU - Solary, E.

AU - Maynadié, M.

AU - Callat, M. P.

AU - Thouret, F.

AU - Monconduit, M.

AU - Vannier, J. P.

N1 - Funding Information: Engagement of preB 1 -ALL cells in the B-lineage growth factors. The SEM cell line indeed is responsive has been debated because CD19 can also be expressed to IL-7,[391and it has also been shown that reduced on myeloid We took great care to assess the CDlO/NEP enzymatic activity may facilitate the presence of other B-lineage markers, and reach a score development of small-cell carcinomas of the lung.‘@] of 2 for that lineage. In the entire series of ALL tested, The high incidence of rearrangement of both IGH we found no case with an isolated expression of CD19 genes, not rarely associated with TCR genes and no other B-marker (data not shown). As in previ-rearrangements could also indicate anomalies in such ous studies[’0*’’a]n d in our own, genotypic analyses regulatory factors as the recombination activating also concur with the fact that these cells are engaged in gene-1 (RAG-1),[45i1n these cells. These concomitent B-cell differentiation, as more than 90% of the cases and conflicting rearrangements could be responsible tested showed rearranged IGH locus, frequently on for the arrest of cell differentiation. both chromosomes 14, while IGL loci were seldom In conclusion, the immunophenotypic subgroup of rearranged. However, more than one third of the cells preB 1-ALL appears to be larger than that merely iden-tested also had either TCRG or TCRB rearrangements tified by chromosome 1 1 alteration^,['*^^.^^] and stands although rarely both. A similar coindicence of IGH out as important to be identified properly through and TCR gene rearrangements has been reported in the immunophenotyping procedures. Presentation fea-SEM cell line.[391 tures may resemble those of other preB ALL, but this These immunophenotypic and genotypic character-series confirms the worse prognosis of this entity, istics nevertheless clearly assign preB 1-ALL to the especially in children. B-lineage, and our series indicates that this immuno- phenotype is not specifically restricted to any particu- lar age-range, as other studies had s ~ g g e s t e d . [ ~ * ~Ãc*kño*w~le dgements We therefore investigated how these cells compared with preB2-ALL cells, which represent the common- est ALL immunophenotype, and also with the less fre- quent T-ALLs. Clinical and biological features at presentation confirmed the relationship between preB 1- ALL and B-lineage ALL, since more numerous differences were found between preB 1- and T-ALL than between preB1-and preB2-ALL. In an earlier series without infants,[38n1 o difference was observed in treatment outcome between 10 CD10-and 254 CD10+ B-lineage ALL cases. In our series, outcome characteristics of the 22 children and 38 adults with preB1 ALL, differed from those of preB2-ALL patients, and we were able to demonstrated the worse prognosis of this disease, more similar to that of T-ALL, especially in children. Cell growth and leukemogenesis in preB 1-ALL could be related to the absence of CDlO expression. CDlOheutral endopeptidase 24.1 I (CD 10NPE) has been reported as an important regulatory molecule, able to inactivate growth factors, or activate growth inhibitory pep tide^.[^^-^' Since preB 1- ALL cells lack this molecule, they could be more responsive to cell We wish to thank Dr T.H. Rabbitts for his kind gift of gene probes, and C. Canipel and P. Marie for their excellent technical assistance. This work was supported by a grant from the Association pour la Recherche sur le Cancer and from the Ligue Nationale Frangaise contre le Cancer (DCpartement de 1’Eure et de la Seine-Maritime). The GEIL is “rCseau INSERM”.

PY - 1998/1/1

Y1 - 1998/1/1

N2 - The less differentiated stage (CD10-) of B-lineage acute lymphoblastic leukaemia (ALL) described as preB1-ALL in the GEIL nomenclature, accounts for less than 10% of ALL. It is classically considered to be associated with translocation (4;11)(q21;q23), and to have a poor prognosis. We report an extensive immunophenotypic, genomic and clinical study of a series of 64 preB-1 ALL patients, representing 6.3% of a cohort of consecutive ALLs. The engagement of preB 1-ALL cells in the B-lineage was confirmed by their B-lineage score, equal to or higher than 2. In addition, more than 90% of the cases tested showed rearranged IGH genes. Translocation (4;11) was the most frequent karyotypic anomaly seen, but only accounted for 24% of the preB1-ALL cases tested. Expression of the myeloid associated antigen CD15 was also found with high incidence in this subset. Clinical and biological features at presentation showed more significant differences between preB1- and T-ALL than between preB1- and preB2-ALL (CD10+). However, outcome characteristics of the 22 children with preB1-ALL confirmed the worse prognosis of this entity.

AB - The less differentiated stage (CD10-) of B-lineage acute lymphoblastic leukaemia (ALL) described as preB1-ALL in the GEIL nomenclature, accounts for less than 10% of ALL. It is classically considered to be associated with translocation (4;11)(q21;q23), and to have a poor prognosis. We report an extensive immunophenotypic, genomic and clinical study of a series of 64 preB-1 ALL patients, representing 6.3% of a cohort of consecutive ALLs. The engagement of preB 1-ALL cells in the B-lineage was confirmed by their B-lineage score, equal to or higher than 2. In addition, more than 90% of the cases tested showed rearranged IGH genes. Translocation (4;11) was the most frequent karyotypic anomaly seen, but only accounted for 24% of the preB1-ALL cases tested. Expression of the myeloid associated antigen CD15 was also found with high incidence in this subset. Clinical and biological features at presentation showed more significant differences between preB1- and T-ALL than between preB1- and preB2-ALL (CD10+). However, outcome characteristics of the 22 children with preB1-ALL confirmed the worse prognosis of this entity.

KW - Acute

KW - Antigens

KW - Blotting

KW - CD10

KW - Genes

KW - Immunoglobulin

KW - Leukemia

KW - Lymphocytic

KW - Receptor

KW - Southern

KW - T-cell

UR - http://www.scopus.com/inward/record.url?scp=6844258882&partnerID=8YFLogxK

U2 - 10.3109/10428199809092688

DO - 10.3109/10428199809092688

M3 - Article

C2 - 9517504

AN - SCOPUS:6844258882

SN - 1042-8194

VL - 28

SP - 329

EP - 342

JO - Leukemia and Lymphoma

JF - Leukemia and Lymphoma

IS - 3-4