Background. Despite treatment results have improved in the past decade, prognosis of ALL in adult age is still dismal. The identification of genetic alterations through gene expression profile (GEP), and deep molecular cytogenetic analysis by SNPs Array, is leading to a more defined characterization of this heterogeneous disease, in order to obtain an optimized risk stratification and develop targeted therapies in different subgroups of ALL. Ph positive, hypodiploidy, and the involvement of MLL gene on chromosome 11, are associated to an unfavourable outcome. Recently, in pediatric ALL, two newly recognized subsets have been identified: 1) the “BCR-ABL like”, a group of cases characterized by very high incidence of relapse, genetic alteration of IKZF1, of VPREB- 1 and a gene expression profile similar to BCR-ABL1 ALL (Mullighan et al.; N Engl J Med 2009); 2) the “ALL with prednisone induced monocytic differentiation”, a novel subtype of childhood B cell precursor recently described (Mejstrikova et al.; personal communication at BFM meeting Bergamo, 2009). However, it is unknown if these two subtypes of ALL are present also in the adult subset. Methods and result. A 43 years woman was hospitalized due to fever and severe asthenia. Peripheral blood count revealed a moderate leucopenia and a severe anemia. A bone marrow biopsy and the immunophenotype signature led to the diagnosis of pre-B ALL. The conventional cytogenetic analysis showed the trisomy of chromosome 8 in 14 out of 20 metaphases. Molecularly, the search for E2A-PBX, BCR-ABL and TEL-AML1 fusion transcripts was negative. After informed consent was obtained, the patient received a prednisone pre-treatment for 8 days, according to our institutional experimental clinical trial based on AIEOP ALL 2000 Protocol. A progressive increasing of white blood cells count was observed, reaching a severe hyperleucocytosis (WBC 140000/mm3) at the end of steroid therapy. A morphological and immunophenotype analysis of peripheral WBC revealed a wide population constituted by CD14 positive mature monocyte cells. Detailed GEP and SNPs Array analysis were performed both before and after steroid treatment. Experiments for cloning the genomic alterations are ongoing and results will be presented. Conclusion. This report supports the presence of a new subset of adult patients with “ALL with prednisone induced monocytic differentiation”, previously described only in the pediatric context. Funding. Work supported by European LeukemiaNet, FIRB 2008, AIRC, AIL, COFIN, University of Bologna and BolognAIL.

A NEW SUBSET OF ADULT B CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) PATIENT WITH PREDNISONE-INDUCED MONOCYTIC DIFFERENTIATION?

PAPAYANNIDIS, CRISTINA;IACOBUCCI, ILARIA;TESTONI, NICOLETTA;BALDAZZI, CARMEN;LONETTI, ANNALISA;OTTAVIANI, EMANUELA;Guadagnuolo V.;CURTI, ANTONIO;PAOLINI, STEFANIA;ABBENANTE, MARIACHIARA;MARTINELLI, GIOVANNI
2009

Abstract

Background. Despite treatment results have improved in the past decade, prognosis of ALL in adult age is still dismal. The identification of genetic alterations through gene expression profile (GEP), and deep molecular cytogenetic analysis by SNPs Array, is leading to a more defined characterization of this heterogeneous disease, in order to obtain an optimized risk stratification and develop targeted therapies in different subgroups of ALL. Ph positive, hypodiploidy, and the involvement of MLL gene on chromosome 11, are associated to an unfavourable outcome. Recently, in pediatric ALL, two newly recognized subsets have been identified: 1) the “BCR-ABL like”, a group of cases characterized by very high incidence of relapse, genetic alteration of IKZF1, of VPREB- 1 and a gene expression profile similar to BCR-ABL1 ALL (Mullighan et al.; N Engl J Med 2009); 2) the “ALL with prednisone induced monocytic differentiation”, a novel subtype of childhood B cell precursor recently described (Mejstrikova et al.; personal communication at BFM meeting Bergamo, 2009). However, it is unknown if these two subtypes of ALL are present also in the adult subset. Methods and result. A 43 years woman was hospitalized due to fever and severe asthenia. Peripheral blood count revealed a moderate leucopenia and a severe anemia. A bone marrow biopsy and the immunophenotype signature led to the diagnosis of pre-B ALL. The conventional cytogenetic analysis showed the trisomy of chromosome 8 in 14 out of 20 metaphases. Molecularly, the search for E2A-PBX, BCR-ABL and TEL-AML1 fusion transcripts was negative. After informed consent was obtained, the patient received a prednisone pre-treatment for 8 days, according to our institutional experimental clinical trial based on AIEOP ALL 2000 Protocol. A progressive increasing of white blood cells count was observed, reaching a severe hyperleucocytosis (WBC 140000/mm3) at the end of steroid therapy. A morphological and immunophenotype analysis of peripheral WBC revealed a wide population constituted by CD14 positive mature monocyte cells. Detailed GEP and SNPs Array analysis were performed both before and after steroid treatment. Experiments for cloning the genomic alterations are ongoing and results will be presented. Conclusion. This report supports the presence of a new subset of adult patients with “ALL with prednisone induced monocytic differentiation”, previously described only in the pediatric context. Funding. Work supported by European LeukemiaNet, FIRB 2008, AIRC, AIL, COFIN, University of Bologna and BolognAIL.
S4
154
154
HAEMATOLOGICA
Papayannidis C.; Iacobucci I.; Testoni N.; Baldazzi C.; Lonetti A.; Ottaviani E.; Guadagnuolo V.; Ferrari A.; Curti A.; Paolini S.; Abbenante M.; Bandini G.; Baccarani M.; Martinelli G.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/154755
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