| ICD-Topo |
C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS |
| ICD-Morpho |
9975/3 Chronic myelogenous leukaemia, BCR-ABL1 positive; Myeloproliferative neoplasm, unclassifiable; Myelodysplastic/myeloproliferative neoplasm, unclassifiable
|
| Atlas_Id |
1659 |
| |  |
| |
| |
A. Conventional karyotype: partial R and G-banded karyotype. The derivative chromosomes of translocations t(9;14)(q33;q32) and t(9;22)(q34;q11) are denoted by solid and dotted arrows, respectively.
B. FISH: representative metaphase hybridized with dual color break-apart IGH probe (Abbott, Rungis, France). A fusion signal is seen on normal chromosome 14 (large arrows), a red signal on derivative chromosome 14 (small solid arrows) and a green signal on derivative chromosome 9 (small dotted arrows).
C. FISH: representative metaphase hybridized with a BCR/ABL ES probe (Abbott). A green signal is seen on a normal chromosome 22 (large arrows), and two fusion signals on derivative chromosomes 9 and 22 (small dotted arrows), confirming the BCR-ABL1 rearrangement with a breakpoint in the mBCR region. A red signal is observed on derivative chromosome 14 (small solid arrows), indicating that the breakpoint of t(9;14) was centromeric to the ABL1 gene in chromosome 9. |
| |
| Disease |
Chronic myeloid leukemia (CML) in B-cell lymphoid blast crisis |
| Phenotype / cell stem origin |
B cell phenotype (CD19, CD10) with 2 aberrant myeloid markers (CD13 and CD33). |
| Etiology | Unknown. |
| Epidemiology | Only one case to date, a 10-year-old male patient (Nadal et al., 2012). |
| Clinics | Lymphadenopathies, enlarged spleen and liver. Central nervous system involvement. |
| Cytology | High WBC with blast cells (44%), myelemia, eosinophilia and basophilia. Bone marrow aspiration showed 60% of undifferentiated blast cells with persistence of the granulocytic lineage. |
| Treatment | The patient was treated according to the European protocol ESPHALL (imatinib, asparaginase, vincristine, vindesine, daunorubicin, aracytine, VP16, ifosfamide, and methotrexate, followed by an allograft). |
| Evolution | After induction, minimal residual disease (MRD) detection by CMF and by molecular analysis was negative, whereas RT-PCR for BCR-ABL1 transcript was still positive. Chromosomal examination showed the presence of one metaphase out of 30 with only the t(9;22)(q34;q11), suggesting that the t(9;14) translocation was a secondary chromosomal abnormality.
Thus, the chemotherapy had eradicated the lymphoblast cells but a CML clone persisted, further supporting the diagnosis of CML in BC.
By 7 months after diagnosis, the patient underwent allogenic stem cell transplantation from his HLA-matched sister. At 2 years post-transplantation, the patient was alive and well. BCR-ABL1 transcript was undetectable (<0.001%). |
| LHX2 deregulation by juxtaposition with the IGH locus in a pediatric case of chronic myeloid leukemia in B-cell lymphoid blast crisis. |
| Nadal N, Chapiro E, Flandrin-Gresta P, Thouvenin S, Vasselon C, Beldjord K, Fenneteau O, Bernard O, Campos L, Nguyen-Khac F. |
| Leuk Res. 2012 Sep;36(9):e195-8. doi: 10.1016/j.leukres.2012.05.013. Epub 2012 Jun 22. |
| PMID 22727509 |
| |
| Lhx2, a LIM homeobox gene, is required for eye, forebrain, and definitive erythrocyte development. |
| Porter FD, Drago J, Xu Y, Cheema SS, Wassif C, Huang SP, Lee E, Grinberg A, Massalas JS, Bodine D, Alt F, Westphal H. |
| Development. 1997 Aug;124(15):2935-44. |
| PMID 9247336 |
| |
| Lhx2 expression in hematopoietic progenitor/stem cells in vivo causes a chronic myeloproliferative disorder and altered globin expression. |
| Richter K, Pinto do O P, Hagglund AC, Wahlin A, Carlsson L. |
| Haematologica. 2003 Dec;88(12):1336-47. |
| PMID 14687986 |
| |
| Identification of a human LIM-Hox gene, hLH-2, aberrantly expressed in chronic myelogenous leukaemia and located on 9q33-34.1. |
| Wu HK, Heng HH, Siderovski DP, Dong WF, Okuno Y, Shi XM, Tsui LC, Minden MD. |
| Oncogene. 1996 Mar 21;12(6):1205-12. |
| PMID 8649822 |
| |
| LH-2: a LIM/homeodomain gene expressed in developing lymphocytes and neural cells. |
| Xu Y, Baldassare M, Fisher P, Rathbun G, Oltz EM, Yancopoulos GD, Jessell TM, Alt FW. |
| Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):227-31. |
| PMID 7678338 |
| |
