102
Letters to the Editor
multidisciplinary use of cytology, cytometry, cytogenetics, FISH, and molecular studies.
Acknowledgments This research is supported by Fondos FEDER, Plan Andaluz n (CTS-0197). de Investigacio
Rau l Garcı´a-Lozano* Jose Servicio de Inmunologı´a Unidad de Gestio n Clı´nica de Laboratorios Clı´nicos Hospital Universitario Virgen del Rocı´o Seville, Spain *Corresponding author. E-mail address: [email protected] http://dx.doi.org/10.1016/j.cancergen.2014.10.006
Supplementary data Supplementary data related to this article can be found at http://dx.doi.org/10.1016/j.cancergen.2014.10.006
References 1. Meyer C, Hofmann J, Burmeister T, et al. The MLL recombinome of acute leukemias in 2013. Leukemia 2013;27:2165e2176. 2. Balgobind BV, Raimondi SC, Harbott J, et al. Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study. Blood 2009;114:2489e2496. 3. Pallisgaard N, Hokland P, Riishøj DC, et al. Multiplex reverse transcription-polymerase chain reaction for simultaneous screening of 29 translocations and chromosomal aberrations in acute leukemia. Blood 1998;92:574e588. 4. DiMartino JF, Ayton PM, Chen EH, et al. The AF10 leucine zipper is required for leukemic transformation of myeloid progenitors by MLL-AF10. Blood 2002;99:3780e3785. 5. Slany RK, Lavau C, Cleary ML. The oncogenic capacity of HRXENL requires the transcriptional transactivation activity of ENL and the DNA binding motifs of HRX. Mol Cell Biol 1998;18:122e129. 6. Van Limbergen H, Poppe B, Janssens A, et al. Molecular cytogenetic analysis of 10;11 rearrangements in acute myeloid leukemia. Leukemia 2002;16:344e351. 7. Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon: IARC Press; 2008. €nholm M, et al. 8. Hjorth-Sørensen B, Pallisgaard N, Gro A novel MLL-AF10 fusion mRNA variant in a patient with acute myeloid leukemia detected by a new asymmetric reverse transcription PCR method. Leukemia 1997;11: 1588e1593. 9. Klaus M, Schnittger S, Haferlach T, et al. Cytogenetics, fluorescence in situ hybridization, and reverse transcriptase polymerase chain reaction are necessary to clarify the various mechanisms leading to an MLL-AF10 fusion in acute myelocytic leukemia with 10;11 rearrangement. Cancer Genet Cytogenet 2003;144:36e43.
Sergio Burillo-Sanz Servicio de Inmunologı´a Unidad de Gestio n Clı´nica de Laboratorios Clı´nicos Hospital Universitario Virgen del Rocı´o Seville, Spain Rosario Morales-Camacho Marı´a Teresa Vargas Estrella Carrillo rez-Soto Inmaculada Pe Unidad de Gestio n Clı´nica de Hematologı´a y Hemoterapia Hospital Universitario Virgen del Rocı´o Seville, Spain
Clonal chromosomal abnormalities in Ph-negative cells in chronic myeloid leukemia: an unusual case evolving to secondary acute myeloid leukemia Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of a chromosomal translocation, t(9;22)(q34;q11), also called the Philadelphia (Ph) translocation, in myeloid progenitors (1). This translocation gives rise to a BCR-ABL1 fusion gene and results in constitutive activation of the ABL1 tyrosine kinase. In recent years, treatment of CML with tyrosine kinase inhibitors (TKIs) induced a cytogenetic remission in a substantial number of cases (2). In a minority of patients, however, clonal cytogenetic abnormalities (CCAs) develop in Ph-negative cells (3). We report the case of a 79-year-old Caucasian male, not previously exposed to genotoxic agents, who presented in December 2005 with hyperleukocytosis and splenomegaly. Peripheral blood count disclosed a hemoglobin level of 10.8 g/dL, a platelet count of 279 109 cells/L, and a white blood cell count of 212 106 cells/L (with 50% neutrophils, 2% lymphocytes, 3% eosinophils, 1% basophils, and a significant myelemia). Bone marrow (BM) aspirate showed myeloid hyperplasia with increased megakaryocytes, of which 25% had hypolobated nuclei and 5% were blasts. Conventional cytogenetic analysis revealed a Ph translocation in 10 of 10 metaphases: 46,XY,t(9;22)(q34;q11). According to the World Health Organization classification, the diagnosis of CML in chronic phase was established (1), and imatinib was started at a dose of 400 mg per day. At 6 months after start of therapy, hematological and partial cytogenetic (30% Ph-positive metaphases) response was achieved, without significant molecular response. At that time, cytogenetic analysis showed the appearance of clonal aberrations in Ph-negative cells. Two unrelated clones were observed, one with a del(5)(q21q34) and one with a del(20)(q12) in 4 of 20 BM metaphases (20%) and 7 of 20 BM metaphases (35%), respectively. BM morphology still showed myeloid hyperplasia and megakaryocytes with hypolobated nuclei, without excess of blasts (
Letters to the Editor
multidisciplinary use of cytology, cytometry, cytogenetics, FISH, and molecular studies.
Acknowledgments This research is supported by Fondos FEDER, Plan Andaluz n (CTS-0197). de Investigacio
Rau l Garcı´a-Lozano* Jose Servicio de Inmunologı´a Unidad de Gestio n Clı´nica de Laboratorios Clı´nicos Hospital Universitario Virgen del Rocı´o Seville, Spain *Corresponding author. E-mail address: [email protected] http://dx.doi.org/10.1016/j.cancergen.2014.10.006
Supplementary data Supplementary data related to this article can be found at http://dx.doi.org/10.1016/j.cancergen.2014.10.006
References 1. Meyer C, Hofmann J, Burmeister T, et al. The MLL recombinome of acute leukemias in 2013. Leukemia 2013;27:2165e2176. 2. Balgobind BV, Raimondi SC, Harbott J, et al. Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study. Blood 2009;114:2489e2496. 3. Pallisgaard N, Hokland P, Riishøj DC, et al. Multiplex reverse transcription-polymerase chain reaction for simultaneous screening of 29 translocations and chromosomal aberrations in acute leukemia. Blood 1998;92:574e588. 4. DiMartino JF, Ayton PM, Chen EH, et al. The AF10 leucine zipper is required for leukemic transformation of myeloid progenitors by MLL-AF10. Blood 2002;99:3780e3785. 5. Slany RK, Lavau C, Cleary ML. The oncogenic capacity of HRXENL requires the transcriptional transactivation activity of ENL and the DNA binding motifs of HRX. Mol Cell Biol 1998;18:122e129. 6. Van Limbergen H, Poppe B, Janssens A, et al. Molecular cytogenetic analysis of 10;11 rearrangements in acute myeloid leukemia. Leukemia 2002;16:344e351. 7. Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon: IARC Press; 2008. €nholm M, et al. 8. Hjorth-Sørensen B, Pallisgaard N, Gro A novel MLL-AF10 fusion mRNA variant in a patient with acute myeloid leukemia detected by a new asymmetric reverse transcription PCR method. Leukemia 1997;11: 1588e1593. 9. Klaus M, Schnittger S, Haferlach T, et al. Cytogenetics, fluorescence in situ hybridization, and reverse transcriptase polymerase chain reaction are necessary to clarify the various mechanisms leading to an MLL-AF10 fusion in acute myelocytic leukemia with 10;11 rearrangement. Cancer Genet Cytogenet 2003;144:36e43.
Sergio Burillo-Sanz Servicio de Inmunologı´a Unidad de Gestio n Clı´nica de Laboratorios Clı´nicos Hospital Universitario Virgen del Rocı´o Seville, Spain Rosario Morales-Camacho Marı´a Teresa Vargas Estrella Carrillo rez-Soto Inmaculada Pe Unidad de Gestio n Clı´nica de Hematologı´a y Hemoterapia Hospital Universitario Virgen del Rocı´o Seville, Spain
Clonal chromosomal abnormalities in Ph-negative cells in chronic myeloid leukemia: an unusual case evolving to secondary acute myeloid leukemia Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of a chromosomal translocation, t(9;22)(q34;q11), also called the Philadelphia (Ph) translocation, in myeloid progenitors (1). This translocation gives rise to a BCR-ABL1 fusion gene and results in constitutive activation of the ABL1 tyrosine kinase. In recent years, treatment of CML with tyrosine kinase inhibitors (TKIs) induced a cytogenetic remission in a substantial number of cases (2). In a minority of patients, however, clonal cytogenetic abnormalities (CCAs) develop in Ph-negative cells (3). We report the case of a 79-year-old Caucasian male, not previously exposed to genotoxic agents, who presented in December 2005 with hyperleukocytosis and splenomegaly. Peripheral blood count disclosed a hemoglobin level of 10.8 g/dL, a platelet count of 279 109 cells/L, and a white blood cell count of 212 106 cells/L (with 50% neutrophils, 2% lymphocytes, 3% eosinophils, 1% basophils, and a significant myelemia). Bone marrow (BM) aspirate showed myeloid hyperplasia with increased megakaryocytes, of which 25% had hypolobated nuclei and 5% were blasts. Conventional cytogenetic analysis revealed a Ph translocation in 10 of 10 metaphases: 46,XY,t(9;22)(q34;q11). According to the World Health Organization classification, the diagnosis of CML in chronic phase was established (1), and imatinib was started at a dose of 400 mg per day. At 6 months after start of therapy, hematological and partial cytogenetic (30% Ph-positive metaphases) response was achieved, without significant molecular response. At that time, cytogenetic analysis showed the appearance of clonal aberrations in Ph-negative cells. Two unrelated clones were observed, one with a del(5)(q21q34) and one with a del(20)(q12) in 4 of 20 BM metaphases (20%) and 7 of 20 BM metaphases (35%), respectively. BM morphology still showed myeloid hyperplasia and megakaryocytes with hypolobated nuclei, without excess of blasts (
