2 by immature lymphocytes resembling L1-FAB subtype with negative myeloperoxidase cytochemistry were observed. Bone Marrow samples had been sent to cytogenetic laboratory for karyotyping and molecular diagnosis of BCR- ABL fusion gene, and the results had been normal karyotype and negative for BCR-ABL (p210) and (p190) fusion gene. A sample had also been sent to Iranian blood transfusion laboratory for Immunophenotyping and the results were as follows. CD10+, CD19+, CD20+, HLA DR+ CD13−, and CD33− and the interpretation were consistent with a pre-B-ALL. After diagnosis on April 2003, the patient had been treated according to the children ALL-BFM conventional protocol (without high dose methotrexate) with prophylactic cranial irradiation (1800 Rad). She had a good response to pred- nisolone and on day 28 BM aspiration had been consistent with hematological remission (<5% blasts), and the results of immunophenotyping had been normal. She had no serious complication during and in between chemotherapy cycles except for few leukopenic episodes that were corrected by G- CSF therapy. She had completed the whole protocol on January 2007 with BM at complete remission, normal CSF, normal Immunophenotyping, and normal uterus and ovaries sono- graphies. CBC results at completion of treatment were as follows. WBC: 5.7∗103/µL, RBC: 3.47 mil/uL, Hemoglobin: 11.6 g/dL, Platelet count: 4∗103/µL, Neutrophile: 67%, lym- phocyte: 30%, Monocyte: 3%. She stayed 3 years out of treatment and at complete remission and had regular visits, and on August 2008 she came for regular checkups and the results of her CBC were as follows. WBC: 69.9∗103/µL, 3.79 mil/uL, Hemoglobin: 11.3 g/dL, Hematocrit: 33.6%, M.C.V: 88.7 fL, M.C.H: 29.8 Pg, M.C.H.C: 33.6 g/dL, Platelet count: 136∗103/µL, Neutro- phile: 60%, Eosinophile: 3%, promyelocyte: 2%, Band: 20%. On physical examination a mild to moderate spleno- megaly had been noticed, and she had been put on antibiotic in case of underlying infection, and bone marrow samples had been taken for cytogenetic, molecular and immunophe- notyping evaluations and another CBC sample had been also taken on October 2008 and the results were as follows. WBC: 82.6∗103/µL, RBC: 366 mil/uL, Hemoglobin: 10.9 g/dL, Hematocrit: 32.4%, M.C.V: 88.5 fL, M.C.H: 29.8 Pg, M.C.H.C: 33.6 g/dL, Platelet count: 152∗103/µL, Neutrophile: 51%, Eosinophile: 2%, Lymphocyte: 16%, Band: 27%, Promyelocyte: 1%, Myelocyte: 2%. The results of molecular evaluation of BM aspirate had been reported negative for t (4, 11), t (1, 19), and t (12, 21) and negative for BCR-ABL (P190) fusion gene and positive for BCR-ABL (P210) fusion gene (TaqMan Technology), and cytogenetic results were positive for Ph-chromosome or t (9; 22). She had been put on imatinib mesylate (Gleevec formerly ST-1571), and there had been a good hematologic and molecular response, and white blood cell count decreased from 76700/uL on April 2008 to 2400/uL on October 2008, Case Reports in Hematology Table 1: Presence of BCR-ABL transcript in sequential Bone Marrow samples. Date November 2008 August 2009 February 2010 July 2010 Status of the disease CP CHR MMR CMR BCR-ABL copy number 11700 30 3 UN detectable CP: chronicphase, (CHR): complete hematology remission, MMR: major molecular response, CMR: complete molecular response. and the BCR-ABL fusion gene decreased from 11700 cpn on May 2008 to undetectable on July 2010. On her last visit on April 2011, she had been under good control no organomegaly, stable condition and still receiving Gleevec, and her CBC results were as follows. WBC: 4.9∗103/µL, RBC: 3.38 mil/uL, Hemoglobin: 10.4 g/dL, Hematocrit: 31.7%, M.C.V: 93.8 fL, M.C.H.C: 32.8 g/dL, Platelet count: 172∗103/µL, Neutrophile: 63%, Eosinophile 1%, lymphocyte: 33.2, Monocyte: 3%. According to the CBC results, the patient had been in complete hematologic remission and on molecular evalua- tion of BCR-ABL fusion gene; the patient had also been in complete molecular response (CMR) status (Table 1). 3. Discussion We describe here a girl with negative Ph(−) pre-B-ALL diagnosed with Ph(+) CML 3 years after completion of therapy and disease-free survival. The main question in this case is whether her leukemia had been secondary to the treatment received or had been actually a relapse of primary leukemia, but since the primary pre-B-ALL in this patient had been Ph(−) the developing CML could be a secondary leukemia most probably a consequence of prior treatment or other environmental exposures that eventually evolved to Ph(+) CML. Second primary cancers represent an important compli- cation of modern chemotherapy and radiotherapy. Therapy- related (tr) leukemias are among the most common sec- ond malignancies in both pediatric and adult populations. Whereas a reasonable amount of data is available regarding the epidemiology, molecular pathogenesis, clinical behavior and response to therapy of second primary acute leukemia, very little is known about therapy-related chronic myeloid leukemia (tr-CML). A better characterization of this entity could increase our understanding about the mechanisms of carcinogenesis, specially the induction of speciﬁc genetic abnormalities, for example, BCR-ABL fusion, following chemotherapy and/or radiotherapy exposure, could facilitate the investigation of the kinetics of the development of CML and also provide a model to study molecular events that might precede its development. The cancer-predisposing syndromes, the detection of BCR-ABL transcripts in healthy individuals, and the in vitro induction of BCR-ABL fusions by ionizing radiation are all discussed in the context of tr-CML. Finally, the need for