DOCSLIB.ORG

The First Report of a Philadelphia Chromosome and BCR/ABL

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The First Report of a Philadelphia Chromosome and BCR/ABL Correspondence 442 a patient treated with etoposide for Langerhans cell histiocytosis. 11 Lakhani S, Davidson RN, Hiwaizi F, Marsden RA. Razoxane and Br J Haematol 1994; 86: 887–889. leukaemia. Lancet 1984; II: 288–289. 8 Wiernik PH, Muse IM. Acute promyelocytic leukemia after treat- 12 Bhavnani M, Al Azzawi S, Liu Yin JA, Lucas GS. Therapy-related ment of malignant glioma in a patient with Von Recklinghausen’s acute promyelocytic leukaemia. Br J Haematol 1994; 86: 231– disease: case report and review of the literature. Leukemia 1996; 232. 10: 178–191. 13 Anticancer Drugs. Antitumor antibiotics. In: De Vita VT Jr, Hell- 9 Snowden JA, Laidlaw ST, Champion AE, Reilly JT. Acute promyel- man S, Rosenberg SA (eds). Cancer. Principles and Practice of ocytic leukaemia after treatment for seminoma with carboplatin. Oncology, 4th edn. JB Lippincott: Philadelphia: 1993; pp. 374– Lancet 1994; 344: 1361. 384. 10 Xue Y, Lu D, Guo Y, Lin B. Specific chromosomal translocations 14 Buckley JD, Gilchrist GS, Ruccione K, Sather HN, Woods WG, and therapy-related leukemia induced by bimolane therapy for Hammon GD. Multiple sclerosis in mothers of children with acute psoriasis. Leukemia Res 1992; 16: 1113–1123. lymphoblastic leukemia. Leukemia 1989; 3: 736–739. The first report of a Philadelphia chromosome and BCR/ABL rearrangement positive myeloproliferative disorder in a child with thrombocythemia TO THE EDITOR adrenalin, arachidonic acid and adenosine diphosphate, and was normal with ristocetin. Chronic myelogenous leukemia (CML) is a chronic myeloprol- Three months later, the patient still had 3000 × 109/l plate- iferative disorder (CMD) characterized by the presence of the lets, WBC 12.2 × 109/l (63% neutrophils, 25% lymphocytes, Philadelphia chromosome (Ph1) in more than 95% of patients. 4% monocytes, 5% basophils, 3% eosinophils) and hemoglo- The Ph1 chromosome is caused by reciprocal translocation bin 13.4 g/dl with no treatment, and began treatment with t(9;22)(q34;q11) which results in rearrangement of the BCR hydroxyurea. and ABL genes. In children under 5 years of age, Ph1 positive Cytogenetic analysis showed a t(9;22). The RT-PCR analy- CML is rare and accounts for 3% of childhood leukemias and sis, performed using published methods,6 revealed the pres- 10% of all CML. ence of P210 (b2a2 junction) (Figure 1a) and P190 (Figure 1b) Essential thrombocythemia (ET) is a chronic myeloprolifer- type of BCR/ABL mRNAs in peripheral blood and bone mar- ative disorder, characterized by the proliferation of a pluripot- row cells. The vast majority of CML cases exhibit a break of ent cell, leading to an increase in the number of platelets. the BCR gene in a 5.8 kb region named M-BCR which, Since ET does not have a distinct cytogenetic or molecular depending on the BCR gene breakpoint, produces two types marker, it has been defined by means of negative criteria, one of mRNA by the junction of exon 3 of the BCR gene to exon 1 of which is the lack of the Ph chromosome and/or BCR/ABL 2 of the ABL gene (b3a2 junction) or of BCR exon 2 to exon rearrangement. However, adult patients have been described 2 of ABL (b2a2 junction) and both chimeric mRNAs encode 1 with a disease resembling ET, but showing Ph chromosome a 210 kDa protein (P210). In our case Southern blot analysis 1–5 and/or BCR/ABL rearrangement. confirmed the BCR/ABL rearrangement with a breakpoint in 1 We report a girl with a Ph -positive and BCR/ABL-positive the M-BCR region (data not shown). CMD presenting as ET. A 5 -year-old female, without previous Recently, Cervantes et al1 have suggested an association relevant history, came to our hospital because of fever up to ° between b3a2 junction and CML with thrombocythemia, in 39.5 C, abdominal pain, vomiting, and diarrhea. She was contrast to Kwong7 who has suggested that this association diagnosed as having intestinal infection and these symptoms may be fortuitous. Our case showed the b2a2 junction con- subsided in 48 h. Physical examination showed splenomegaly firmed by Southern blot analysis and could support the last 3 cm below the left costal margin and hepatomegaly 1 cm hypothesis. In addition to P210 mRNA, there was a P190 below the costal margin, with no lymphadenopathies or other BCR/ABL hybrid mRNA. The presence of low levels of mRNA abnormal signs. Peripheral blood counts showed: hemoglobin of the P190 protein in most cases of P210 BCR/ABL positive 13.6 g/dl, WBC 8.4 × 109/l (57% neutrophils, 38% lympho- patients has been recently described.6 cytes, 5% basophils) and 2200 × 109/l platelets. Neutrophil Sporadic cases have been reported of adult patients with alkaline phosphatase score was 40/400, ferritin 12 ng/ml, ␮ thrombocythemia higher than 1000 × 109/l and moderate leu- transferrin 325 g/dl, transferrin saturation 18%, and all other 1 biochemical parameters were normal. The bone marrow kocytosis, who presented Ph chromosome and/or BCR/ABL rearrangement.1–5 To our knowledge, the case described here aspirate showed a marked megakaryocytic hyperplasia (many 1 megakaryocytes, small in size, with hypolobulated nuclei), is the first pediatric patient with a Ph -positive CMD aggregates of platelet debris and 3–5% blast; the myeloid and presenting as ET. erythroid series were conserved. The study of platelet aggre- These cases might be considered as at the initial stage of gation showed a decrease of the aggregation with collagen, CML, although from the clinical point of view would fit with real ETs with a Philadelphia chromosome. However, the Poly- cythemia Vera Study Group establishes the presence of t(9;22) of the BCR/ABL hybrid gene as an exclusion criteria for the Correspondence: A Villegas, Department of Haematology, Hospital 1 Clinico San Carlos, Calle Pofesor Martin Lagos S/N, 28040, Madrid, ET diagnosis. It has been suggested that Ph positive throm- Spain bocythemias have clinicopathological characteristics different Received 12 June 1997; accepted 18 November 1997 from those of CML, mainly higher frequency in females, Correspondence 443 Figure 1 (a) cDNA amplification by RT-PCR for study of P210 mRNA. Lane 1: molecular weight marker (phiX174 DNA digested with HaeIII); lane 2: patient with P210 negative acute lymphoblastic leukaemia; lane 3: study in bone marrow of the patient described, showing P210 (b2a2 junction) positivity; lane 4: study in peripheral blood of the patient described, showing P210 (b2a2 junction) positivity; lane 5: positive control (CML positive for the b3a2 junction of the P210 type of BCR/ABL); lane 6: negative control; lane 7, 8 and 9: amplification of non-rearranged ABL genes from the same cDNAs as lanes 2, 3 and 4 which were used as internal controls. (b) cDNA amplification by RT-PCR for study of P190 type of BCR/ABL mRNA. Lane 1: molecular weight marker (phiX174 DNA digested with HaeIII); lane 2: patient with P190 positive acute lymphoblastic leukaemia (ALL), used as positive control; lane 3 and 4: P190 negative patients with ALL; lane 5: study in bone marrow of the patient described, showing P190 positivity; lane 6: negative control; lanes 7, 8 and 9: amplification of non-rearranged ABL genes from the same cDNAs as lanes 3, 4 and 5 which were used as internal controls. absence of splenomegaly and variable clinical evolution.2,4,5 E Anguita11Department of Haematology, and It will be necessary to describe and follow-up more such cases F Valverde22Paediatric Department, Hospital ´ to see whether they have clinico-biological features in com- FA Gonzalez1 Universitario San Carlos, mon and behave differently to typical CML. C Gil2 and Department of Human Genetics, ´ M Mateo1 Hospital Ramony Cajal, MT Ferro3 Madrid, Spain Acknowledgements A Villegas1 This work has been supported in part by the grant FIJC-96/ESP ´ from the Jose Carreras International Leukemia Foundation, Spain. Correspondence 444 References BCR rearrangement in apparent essential thrombocythaemia. Br J Haematol 1993; 85: 625–626. 1 Cervantes F, Colomer D, Vives-Corrons JL, Rozman C, Montserrat 5 Stoll DB, Peterson P, Exten R, Laszlo J, Pisciotta AV, Ellis JT, White E. Chronic myeloid leukemia with thrombocythemic onset: a CML P, Vaidya K, Bozdech M, Murphy S. Clinical presentation and subtype with distinct hematological and molecular features? Leu- natural history of patients with essential thrombocythemia and the kemia 1996; 10: 1241–1243. Philadelphia chromosome. Am J Hematol 1988; 27: 77–83. 2 Kwong YL, Chiu EKW, Liang RHS, Chan V, Chan TK. Essential 6 Saglio G, Pane F, Gottardi E, Frigeri F, Buonaiuto M, Guerrasio thrombocythemia with BCR/ABL rearrangement. Cancer Genet A, De Micheli D, Parziale A, Fornaci MN, Martinelli G, Salvatore Cytogenet 1996; 89: 74–76. F. Consistent amounts of acute leukemia-associated P190BCR/ABL 3 Michiels JJ, Prins ME, Hagermeijer A, Brederoo P, van der Meulen transcripts are expressed by chronic myelogenous leukemia J, van Vliet HHD, Abels J. Philadelphia chromosome-positive patients at diagnosis. Blood 1996; 87: 1075–1080. thrombocythemia and megakaryoblast leukemia. Am J Clin Pathol 7 Kwong YL. Association between b3a2 BCR/ABL fusion and 1987; 88: 645–652. chronic myeloid leukemia with thrombocythemic onset: fortuitous 4 Richards EM, Bloxham DM, Nacheva E, Marcus RE, Green AR. or real? Leukemia 1997; 11: 617–618. COMMENT ON PUBLISHED PAPER Discordant erythropoiesis in CML TO THE EDITOR plicities should be observed with different recombinant cyto- kines but otherwise identical culture conditions.4 We enjoyed reading the recent leading article by Clarkson et Finally, Clarkson et al1 have highlighted the response of al1 concerning ‘New understanding of the pathogenesis of normal and CML progenitor cells to c-kit ligand (KL). In both CML: a prototype of early neoplasia’ and broadly agree with cases, addition of KL to Epo increased the size of the colonies their ‘Discordant Maturation’ hypothesis.
Load more

Recommended publications
  • Clinical Outcome in Pediatric Patients with Philadelphia Chromosome
    cancers Article Clinical Outcome in Pediatric Patients with Philadelphia Chromosome Positive ALL Treated with Tyrosine Kinase Inhibitors Plus Chemotherapy—The Experience of a Polish Pediatric Leukemia and Lymphoma Study Group Joanna Zawitkowska 1,*, Monika Lejman 2 , Marcin Płonowski 3, Joanna Bulsa 4, Tomasz Szczepa ´nski 4 , Michał Romiszewski 5, Agnieszka Mizia-Malarz 6, Katarzyna Derwich 7, Gra˙zynaKarolczyk 8, Tomasz Ociepa 9, Magdalena Cwikli´ ´nska 10, Joanna Treli´nska 11, Joanna Owoc-Lempach 12, Ninela Irga-Jaworska 13, Anna Małecka 13, Katarzyna Machnik 14, Justyna Urba ´nska-Rakus 14, Radosław Chaber 15 , Jerzy Kowalczyk 1 and Wojciech Młynarski 11 1 Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, 20-059 Lublin, Poland; [email protected] 2 Laboratory of Genetic Diagnostics, Medical University of Lublin, 20-059 Lublin, Poland; [email protected] 3 Department of Pediatric Oncology, Hematology, Medical University of Bialystok, 15-089 Bialystok, Poland; [email protected] 4 Department of Pediatrics, Hematology and Oncology, Medical University of Silesia, 40-752 Katowice, Poland; [email protected] (J.B.); [email protected] (T.S.) 5 Department of Hematology and Pediatrics, Medical University of Warsaw, 02-091 Warsaw, Poland; [email protected] 6 Department of Pediatric Oncology, Hematology and Chemotherapy, Medical University of Silesia, 40-752 Katowice, Poland; [email protected] 7 Department of Pediatric Oncology, Hematology and
    [Show full text]
  • Philadelphia Chromosome Unmasked As a Secondary Genetic Change in Acute Myeloid Leukemia on Imatinib Treatment
    Letters to the Editor 2050 The ELL/MLLT1 dual-color assay described herein entails 3Department of Cytogenetics, City of Hope National Medical Center, Duarte, CA, USA and co-hybridization of probes for the ELL and MLLT1 gene regions, 4 each labeled in a different fluorochrome to allow differentiation Cytogenetics Laboratory, Seattle Cancer Care Alliance, between genes involved in 11q;19p chromosome translocations Seattle, WA, USA E-mail: [email protected] in interphase or metaphase cells. In t(11;19) acute leukemia cases, gain of a signal easily pinpoints the specific translocation breakpoint to either 19p13.1 or 19p13.3 and 11q23. In the References re-evaluation of our own cases in light of the FISH data, the 19p breakpoints were re-assigned in two patients, underscoring a 1 Harrison CJ, Mazzullo H, Cheung KL, Gerrard G, Jalali GR, Mehta A certain degree of difficulty in determining the precise 19p et al. Cytogenetic of multiple myeloma: interpretation of fluorescence in situ hybridization results. Br J Haematol 2003; 120: 944–952. breakpoint in acute leukemia specimens in the context of a 2 Thirman MJ, Levitan DA, Kobayashi H, Simon MC, Rowley JD. clinical cytogenetics laboratory. Furthermore, we speculate that Cloning of ELL, a gene that fuses to MLL in a t(11;19)(q23;p13.1) the ELL/MLLT1 probe set should detect other 19p translocations in acute myeloid leukemia. Proc Natl Acad Sci 1994; 91: 12110– that involve these genes with partners other than MLL. Accurate 12114. molecular classification of leukemia is becoming more im- 3 Tkachuk DC, Kohler S, Cleary ML.
    [Show full text]
  • Treatment of Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
    Acute lymphoblastic leukemia Treatment of Philadelphia chromosome positive acute lymphoblastic leukemia O.G. Ottmann ABSTRACT Patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) are now Department of Internal Medicine, routinely treated front-line with tyrosine kinase inhibitors (TKI), usually combined with chemotherapy, Hematology-Oncology, with unequivocal evidence of clinical benefit. The first-generation TKI imatinib induces hematologic Goethe University, Frankfurt am remissions in nearly all patients, but these are rarely maintained unless patients undergo allogeneic Main, Germany stem cell transplantation (alloSCT), the current gold standard of curative therapy. The more potent sec - ond- and third-generation TKI display greater clinical efficacy based on molecular response data and Correspondence: clinical outcome parameters. It is still uncertain whether they may obviate the need for alloSCT in Oliver G. Ottmann some adult patients who achieve a deep molecular response, whereas this appears to often be the case E-mail: [email protected] in pediatric patients. Which chemotherapy regimen is best suited in combination with the individual TKI in different subsets of patients is being explored in ongoing studies. Molecular analyses to measure MRD levels, detect BCR-ABL kinase domain mutations, or further subclassify patients according to Hematology Education: additional genomic aberrations has become increasingly important in clinical patient management. A the education program for the variety
    [Show full text]
  • Acute Myeloid Leukemia with Both Meakaryoblastic & Basophilic
    Hematology & Transfusion International Journal Case Report Open Access Acute myeloid leukemia with both meakaryoblastic & basophilic differentiation Abstract Volume 5 Issue 2 - 2017 Acute myeloid leukemia with Megakaryoblastic and Basophilic differentiation and Mariam Al Ghazal, Mohammed Dastagir AH CML with concurrent Megakaryoblastic and Basophilic Blast crisis are very rare diseases with only few reported cases in the literature. Diagnosis of this leukemia with Khan Department of Hematopathology and Cytogenetic, Dammam two types of blasts of the same lineage can be very challenging and morphology alone regional laboratory, Saudi Arabia is not sufficient especially when the morphology is not classical. Flowcytometry and cytogenetic studies are important to establish the diagnosis. Here we report a case Correspondence: Mariam Al Ghazal, Department of of AML with Megakaryoblastic & basophilic differentiation & Positive Philadelphia Hematopathology and Cytogenetic, Dammam regional chromosome by FISH. laboratory, Saudi Arabia, Email [email protected] Keywords: leukemia, megakaryoblastic, basophilic, blast crisis, diagnosis Received: August 01, 2017 | Published: August 30, 2017 Abbreviations: AMLs, acute myeloid leukemias; CML, published case of similar morphological combination but negative for chronic myelogenous leukemia ph chromosome was published by Sreedharanunni et al.4 Introduction Case presentation Basophilia is commonly associated with Chronic Myelogenous A 54-year-old Egyptian man, who presented with Anemia and Leukemia, notably in the accelerated phase or during blast crisis. It lytic lesion as evident by x-ray, was referred to our institution for is also associated with other myeloproliferative neoplasms. However, Flowcytometry. Peripheral Blood shows WBC 1717×/ul. Hb- 6.7g/dl its association with acute leukemia is very rare and is described and Platelets count 82,000/ul.
    [Show full text]
  • PZ003 Bosutinib Pregnancy Mpls Layout Tc06
    Please note that this summary only contains information from the full scientific article: https://www.futuremedicine.com/doi/10.2217/ijh-2020-0004View Scientific Article Pregnancy outcomes in people who took bosutinib Date of summary: May 2020 Analysis end date: February 28, 2018 The full title of this article: Pregnancy outcomes in patients treated with bosutinib This study drug is approved to treat the condition This analysis reports the results of a number of studies. under study that is discussed in this analysis. The results of this analysis might be dierent from the results of other studies that the researchers look at. Researchers must look at the results of many types of studies to understand whether a study drug More information can be found in the scientific article of this works, how it works, and whether it is safe to analysis, which you can access here: https://www.futuremedicine.com/doi/10.2217/ijh-2020-0004View Scientific Article prescribe to patients Bosutinib <boh-SOO-tih-nib> Imatinib <ih-MA-tih-nib> Dasatinib <da-SA-tih-nib> Nilotinib <ny-LOH-tih-nib> Chronic myeloid leukemia Tyrosine kinase inhibitor < KRAH-nik MY-eh-loyd loo-KEE-mee-ah> <TY-ruh-seen KY-nays in-HIH-bih-ter> What did this analysis look at? • Chronic myeloid leukemia (CML for short) is a type of cancer that aects white blood cells. It tends to progress slowly over many years. – CML is caused by the formation of a gene called BCR-ABL, which causes the cancer cells to increase in number. – Genes are segments of DNA* and are found in structures called chromosomes within each cell of the body.
    [Show full text]
  • Chromosome Translocations and Human Cancer1
    [CANCER RESEARCH 46, 6019-6023, December 1986] Perspectives in Cancer Research Chromosome Translocations and Human Cancer1 Carlo M. Croce2 The Wistar Institute, Philadelphia, Pennsylvania 19104 The cytogenetic analysis of human cancer cells by standard rearrangement, somatic cell hybrids between mouse myeloma and by high resolution banding techniques indicates that more cells and Burkitt's lymphoma cells with the t(8; 14) chromosome than 90% of human malignancies carry clonal cytogenetic translocation were produced and analyzed with probes specific changes (1). The discovery of the Philadelphia chromosome in for the genes for the variable and constant regions of the human the neoplastic cells of patients with CML3 (2) and the subse heavy chains (13). The results of this analysis indicated that the quent findings that the great majority of human hematopoietic human heavy chain locus is split at various sites by the chro malignancies carry specific chromosomal alterations (3, 4) have mosomal translocation and that the genes for the variable suggested that such nonrandom chromosomal changes may be regions translocate to the involved chromosome 8 (8q-), while involved in the pathogenesis of human malignancies. This view, the genes for the constant regions remain on the involved however, was not shared by many investigators outside the field chromosome 14 (14q+) (13). Analysis of the hybrids for the of cancer cytogenetics, who regarded such chromosomal alter expression of human heavy chains also indicated that the ex ations as epiphenomena of the neoplastic process. pressed human heavy chain locus in Burkitt's lymphoma resides Recent developments in the analyses of genes involved in the on the normal chromosome 14 (13).
    [Show full text]
  • Philadelphia-Positive Acute Myeloblastic Leukemia: a Rare Entity Definition Genetics Mechanism Epidemiology Clinical Features Im
    Commentary iMedPub Journals Journal of Neoplasm 2016 http://www.imedpub.com/ ISSN 2576-3903 Vol.1 No.1:2 DOI: 10.217672576-3903.100002 Philadelphia-Positive Acute Myeloblastic Leukemia: A Rare Entity Smeeta Gajendra1 and Sahoo MK2 1Department of Pathology and Laboratory Medicine, Gurgaon, Haryana, India 2Department of Nuclear Medicine, All India Institute of Medical Science, New Delhi, India Corresponding author: Smeeta Gajendra, Associate Consultant, Department of Pathology and Laboratory Medicine, Medanta-The Medicity, Sector - 38, Gurgaon, Haryana 122 001, India, Tel: 09013590875, Fax: +91- 124 4834 111; E-mail: [email protected] Received date: March 13, 2016; Accepted date: April 06, 2016; Published date: April 12, 2016 Citation: Gajendra S, Sahoo MK. Philadelphia-Positive Acute Myeloblastic Leukemia: A Rare Entity. J Neoplasm 2016, 1:1 Definition transformation. In the ABL portion, these domains are the SH1 (tyrosine kinase), SH2 and actin-binding domains and in the Philadelphia positive (Ph+) Acute Myeloblastic Leukemia BCR portion, they are the coiled-coil oligomerization domain (AML) is an acute onset neoplasm of myeloblasts in which the comprised between amino acids (aa) 1-63, the tyrosine at blasts harbor BCR/ABL translocation in the absence of a clinical position 177 (GRB-2 binding site) and the phosphor serine/ history of chronic phase or accelerated phase chronic myeloid threonine rich SH2 binding domain. The increased tyrosine leukemia (CML) and a lack of clinical and laboratory features of kinase activity of BCR-ABL fusion protein results in CML, such as splenomegaly and basophilia. phosphorylation of several cellular substrates and auto- phosphorylation of BCR-ABL, which in turn induces Keywords: Philadelphia chromosome; BCR/ABL; Acute recruitment and binding of a number of adaptor molecules myeloid leukemia and proteins.
    [Show full text]
  • Secondary Philadelphia Chromosome Acquired During Therapy of Acute Leukemia and Myelodysplastic Syndrome
    Modern Pathology (2018) 31:1141–1154 https://doi.org/10.1038/s41379-018-0014-x ARTICLE Secondary Philadelphia chromosome acquired during therapy of acute leukemia and myelodysplastic syndrome 1 1 2 1 2 Habibe Kurt ● Lan Zheng ● Hagop M. Kantarjian ● Guilin Tang ● Farhad Ravandi-Kashani ● 2 1 1 1 1 3 Guillermo Garcia-Manero ● Zimu Gong ● Hesham M. Amin ● Sergej N. Konoplev ● Mark J. Routbort ● Xin Han ● 1 1 1 Wei Wang ● L. Jeffery Medeiros ● Shimin Hu Received: 3 October 2017 / Revised: 29 November 2017 / Accepted: 3 December 2017 / Published online: 14 February 2018 © United States & Canadian Academy of Pathology 2018 Abstract The Philadelphia chromosome resulting from t(9;22)(q34;q11.2) or its variants is a defining event in chronic myeloid leukemia. It is also observed in several types of de novo acute leukemia, commonly in B lymphoblastic leukemia, and rarely in acute myeloid leukemia, acute leukemia of ambiguous lineage, and T lymphoblastic leukemia. Acquisition of the Philadelphia chromosome during therapy of acute leukemia and myelodysplastic syndrome is rare. We reported 19 patients, including 11 men and 8 women with a median age of 53 years at initial diagnosis. The diagnoses at initial presentation were = = = 1234567890();,: acute myeloid leukemia (n 11), myelodysplastic syndrome (n 5), B lymphoblastic leukemia (n 2), and T lymphoblastic leukemia (n = 1); no cases carried the Philadelphia chromosome. The Philadelphia chromosome was detected subsequently at relapse, or at refractory stage of acute leukemia or myelodysplastic syndrome. Of 14 patients evaluated for the BCR-ABL1 transcript subtype, 12 had the e1a2 transcript. In 11 of 14 patients, the diseases before and after emergence of the Philadelphia chromosome were clonally related by karyotype or shared gene mutations.
    [Show full text]
  • The Cytogenetics of Hematologic Neoplasms 1 5
    The Cytogenetics of Hematologic Neoplasms 1 5 Aurelia Meloni-Ehrig that errors during cell division were the basis for neoplastic Introduction growth was most likely the determining factor that inspired early researchers to take a better look at the genetics of the The knowledge that cancer is a malignant form of uncon- cell itself. Thus, the need to have cell preparations good trolled growth has existed for over a century. Several biologi- enough to be able to understand the mechanism of cell cal, chemical, and physical agents have been implicated in division became of critical importance. cancer causation. However, the mechanisms responsible for About 50 years after Boveri’s chromosome theory, the this uninhibited proliferation, following the initial insult(s), fi rst manuscripts on the chromosome makeup in normal are still object of intense investigation. human cells and in genetic disorders started to appear, fol- The fi rst documented studies of cancer were performed lowed by those describing chromosome changes in neoplas- over a century ago on domestic animals. At that time, the tic cells. A milestone of this investigation occurred in 1960 lack of both theoretical and technological knowledge with the publication of the fi rst article by Nowell and impaired the formulations of conclusions about cancer, other Hungerford on the association of chronic myelogenous leu- than the visible presence of new growth, thus the term neo- kemia with a small size chromosome, known today as the plasm (from the Greek neo = new and plasma = growth). In Philadelphia (Ph) chromosome, to honor the city where it the early 1900s, the fundamental role of chromosomes in was discovered (see also Chap.
    [Show full text]
  • How I Diagnose and Manage Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia
    REVIEW ARTICLE How I diagnose and manage Philadelphia chromosome-like acute lymphoblastic Ferrata Storti Foundation leukemia Avraham Frisch 1 and Yishai Ofran 1,2 1Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, and 2Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel Haematologica 2019 ABSTRACT Volume 104(11):2135-2143 dvances in our understanding of mechanisms of leukemogenesis and driver mutations in acute lymphoblastic leukemia (ALL) lead to a Amore precise and informative sub-classification, mainly of B-cell ALL. In parallel, in recent years, novel agents have been approved for the therapy of B-cell ALL, and many others are in active clinical research. Among the newly recognized disease subtypes, Philadelphia-chromosome- like ALL is the most heterogeneous and thus, diagnostically challenging. Given that this subtype of B-cell ALL is associated with a poorer prognosis, improvement of available therapeutic approaches and protocols is a burn - ing issue. Herein, we summarize, in a clinically relevant manner, up-to-date information regarding diagnostic strategies developed for the identification of patients with Philadelphia-chromosome-like ALL. Common therapeutic dilemmas, presented as several case scenarios, are also discussed. It is cur - rently acceptable that patients with B-cell ALL, treated with an aim of cure, irrespective of their age, be evaluated for a Philadelphia-chromosome-like signature as early as possible. Following Philadelphia-chromosome-like recognition, a higher risk of resistance or relapse must be realized and treat - ment should be modified based on the patient's specific genetic driver and Correspondence: clinical features. However, while active targeted therapeutic options are YISHAI OFRAN limited, there is much more to do than just prescribe a matched inhibitor to [email protected] the identified mutated driver genes.
    [Show full text]
  • (Q11.23), Tetrasomy 8 and Trisomy 19 in a Blast Crisis-Chronic
    Wafa et al. Molecular Cytogenetics (2015) 8:98 DOI 10.1186/s13039-015-0204-x CASE REPORT Open Access Masked inv dup(22)(q11.23), tetrasomy 8 and trisomy 19 in a blast crisis-chronic myeloid leukemia after interrupted Imatinib-treatment Abdulsamad Wafa1, Suher Almedani1, Thomas Liehr2 and Walid Al-Achkar1* Abstract Background: The Philadelphia (Ph) chromosome, or derivative chromosome 22 [der(22)], is a product of the reciprocal translocation t(9;22). It is the hallmark of chronic myelogenous leukemia (CML). It results in juxtaposition of the 5’ part of the BCR gene on chromosome 22 to the 3’ part of the ABL1 gene on chromosome 9. During CML progression 60–80 % of the cases acquire additional genetic changes. Blast crisis (BC) is characterized by the rapid expansion of a population of differentiation arrested blast cells (myeloid or lymphoid cells population), often presenting with secondary chromosomal abnormalities. Here we report an unusual CML-BC case with acquired secondary chromosomal aberrations observed after the patient had to interrupt a successful Imatinib treatment for overall 16 months. Case presentation: A complete cytogenetic and molecular cytogenetic analysis were performed and application of molecular genetic methods such as reverse transcription polymerase chain reaction (RT-PCR) finally characterized a complex karyotype including an inv dup(22)(q11.23), tetrasomy 8 and trisomy 19. Conclusions: Here we report the first case of a BC after successfully initiated and suddenly interrupted Imatinib treatment. Changes present after such an instant indicate for a rapid progression after Imatinib is no longer suppressing the disease. Keywords: Chronic myeloid leukemia, Philadelphia chromosome, inv dup(22)(q11.23), Tetrasomoy 8, Clonal evolution, Prognostic factors Background that encodes a constitutively activated protein tyrosine Chronic myeloid leukemia (CML) is a myeloprolifera- kinase.
    [Show full text]
  • Common and Individually Specific Chromosomal Characteristics
    [CANCER RESEARCH 36, 398-404, February 1976] Common and Individually Specific Chromosomal Characteristics of Cultured Human Melanoma1 Peter B. McCulloch,2 Peter B. Dent, Paula R. Hayes, and Shuen-Kuei Liao Hamilton Clinic, Ontario Cancer Treatment and Research Foundation [P. B. M., P. B. D., P. R. H., S. K. L.], and Departments of Medicine [P. B. M., P. R. H.] and Pediatrics [P. B. D. , 5. K. L.J, McMaster University, Hamilton, Ontario, Canada SUMMARY any histological class of tumor. However, with the advent of individual chromosome identification, this whole area ne Since individual chromosomes can be accurately identi quires further study. fied by new banding techniques, atebnin fluorescence was used for chromosome analysis in six cell lines and two MATERIALS AND METHODS primary outgrowths derived from human malignant mela noma. Gross aneuploidy was seen in all specimens, but Eight different cultures obtained from human malignant each culture contained at least 1 distinctive marker chromo melanoma were studied. Their sources, individual chromo some specific for that cell line in 87 to 100% of metaphases. somal characteristics, and modal distribution of 50 meta One of the primary explants contained a marker that was phases from each culture are summarized in Table 1. demonstrable in fresh tissue and persisted through 2 weeks M-6 and 73-61 were primary explants established from of culture. The same marker was found in all metaphases metastatic malignant melanomas in our laboratory. The tis from 2 different metastases, but skin fibroblasts from the sue was minced and trypsinized. Some cultures were ob same patient had a normal chromosome complement.
    [Show full text]