• Faris Q Alenzi
  • Ali M. Al-Amri
  • Fahad G. B. Alanazi
  • Waleed Tamimi
  • Ayad Alanazi
  • Awwad K. Alenezy
  • Farhan Al- Swailmi


Background: The cyto-genetic hallmark of chronic myeloid leukaemia (CML), the Philadelphiachromosome (Ph), is the first consistent chromosomal abnormality that has been associated to a certaincancer type. In CML, Philadelphia chromosome is present leading to resistance to cell death and rapidproliferation. The aim of this study is to evaluate the different responses, toxicity and survival of SaudiCML patients to imatinib mesylate. Methods: All newly diagnosed CML patients who were treatedwith imatinib were included in this study. We investigated haematological, and molecular and cytogenetic responses by CBC, FISH and RT-PCR respectively. Cell proliferation and apoptosis wereassayed using AUC and TUNEL respectively. Results: Of the 12 cases, 9 (75%) were males and 3(25%) were female. Four (33%) of the cases were diagnosed incidentally and 8 cases (67%) presentedmainly with fatigue (75%), fever (58%), and splenomegaly (83%). Signs of bleeding and rashes wererare at presentation. The majority of patients had low risk (8, 67%), and 33% had intermediate risk; butnone of them had high risk CML. At the last follow up, 11 (92%) were in remissions. One patient (8%)was in remission after 3 years, 4 (33%) were in remission after 6 years, one was in remission after 7years and 5 (42%) were in remission after 10 years. Only one patient had incomplete major molecularresponse (MMR) to imatinib after 12 years. The majority of the patients (10, 83%) were in MMR after6 years and 42% of them were in MMR after 10 years of therapy. Adverse effects of imatinib were notreported by the patients. Imatinib treatment resulted in the reduction of proliferation and induction ofapoptosis of CML CFU-GM cells. Conclusion: Imatinib mesylate is capable of treating Philadelphiachromosome-positive CP-CML without any adverse effects.Keywords: Imatinib, Philadelphia, CML, responses


Nowell PC, Hungerford DA. Chromosome studies in human

leukemia. II. Chronic granulocytic leukemia. J Natl Cancer Inst


Gorusu M, Benn P, Li Z, Fang M. On the genesis and prognosis

of variant translocations in chronic myeloid leukemia. Cancer

Genet Cytogenet 2007;173(2):97–106.

Bose S, Deininger M, Gora-Tybor J, Goldman JM, Melo JV. The

presence of typical and atypical BCR-ABL fusion genes in

leukocytes of normal individuals: biologic significance and

implications for the assessment of minimal residual disease.

Blood 1998;92(9):3362–7.

Deininger MW, Goldman JM, Melo JV. The molecular biology

of chronic myeloid leukemia. Blood 2000;96:3343–56.

Mandanas RA, Boswell HS, Lu L, Leibowitz D. BCR-ABL

confers growth factor independence upon a murine myeloid cell

line. Leukemia 1992;6:796–800.

Sirard C, Laneuville P, Dick J. Expression of bcr-abl abrogates

factor-dependent growth of human hematopoietic M07E cells by

an autocrine mechanism. Blood 1994;83:1575–85.

Cortez D, Kadlec L, Pendergast AM. Structural and signaling

requirements for BCR-ABL-mediated transformation and

inhibition of apoptosis. Mol Cell Biol 1995;15:5531–41.

Daley GQ, Baltimore D. Transfection of an interleukin 3-

dependent hematopoietic cell line by the chronic myelogenous

leukemia-specific P210 protein. Proc Natl Acad Sci USA


Udomsakdi C, Eaves CJ, Swolin B, Reid DS, Barnett MJ, Eaves

AC. Rapid decline of chronic myeloid leukemia cells in longterm culture due to a defect at the stem cell level. Proc Natl Acad

Sci USA 1992;89:6192–6.

Marley SB, Lewis JL, Scott MA, Goldman JM, Gordon MY.

Evaluation of “discordant maturation” in chronic myeloid

leukaemia using cultures of primitive progenitor cells and their

production of clonogenic progeny (CFU-GM). Br J Haematol


Chasty RC, Lucas GS, Owen-Lynch PJ, Pierce A, Whetton AD.

Macrophage inflammatory protein-1 alpha receptors are present

on cells enriched for CD34 expression from patients with chronic

myeloid leukemia. Blood 1995;86:4270–7.

Cashman JD, Eaves CJ, Sarris AH, Eaves AC. MCP-1, not MIP-

alpha, is the endogenous chemokine that cooperates with TGFbeta to inhibit the cycling of primitive normal but not leukemic

(CML) progenitors in long-term human marrow cultures. Blood


Gordon MY, Dowding CR, Riley GP, Goldman JM, Greaves

MF. Altered adhesive interactions with marrow stroma of

haematopoietic progenitor cells in chronic myeloid leukaemia.

Nature 1987;328:342–4.

Verfaillie CM, McCarthy JB, McGlave PB. Mechanisms

underlying abnormal trafficking of malignant progenitors in

chronic myelogenous leukemia. Decreased adhesion to stroma

and fibronectin but increased adhesion to the basement

membrane components laminin and collagen type IV. J Clin

Invest 1992;90:1232–41.

Vijayan KV, Advani SH, Zingde SM. Chronic myeloid leukemic

granulocytes exhibit reduced and altered binding to P-selectin:

modification in the CD15 antigens and sialylation. Leuk Res


Rowley JD. A new consistent chromosomal abnormality in

chronic myelogenous leukaemia identified by quinacrine

fluorescence and Giemsa staining. Nature 1973;243:290–3.

Bartram CR, de Klein A, Hagemeijer A, van Agthoven T, Geurts

vanKessel A, Bootsma D, et al. Translocation of c-Abl oncogene

correlates with the presence of a Philadelphia chromosome in

chronic myelocytic leukaemia. Nature 1983;306:277–80.

Dasmahapatra G, Nguyen TK, Dent P, Grant S. Adaphostin and

bortezomib induce oxidative injury and apoptosis in imatinib

mesylate-resistant hematopoietic cells expressing mutant forms

of Bcr/Abl. Leuk Res 2006;30(10):1263–72.

Borthakur G, Kantarjian H, Daley G, Talpaz M, O'Brien S,

Garcia-Manero G, Giles F, et al. Pilot study of onafarnib, a

farnesyl transferase inhibitor, in patients with chronic myeloid

leukemia in the chronic or accelerated phase that is resistant or

refractory to imatinib therapy. Cancer 2006;106:346–52.

Jorgensen HG, Allan EK, Mountford JC, Richmond L, Harrison

S, Elliott MA, et al. Enhanced CML stem cell elimination in vitro

by bryostatin priming with imatinib mesylate. Exp Hematol


Shah NP, Tran C, Lee FY, Chen P, Norris D, Sawyers CL.

Overriding imatinib resistance with a novel ABL kinase inhibitor.

Science 2004;305(5682):399–401.

Mukai M, Che XF, Furukawa T, Sumizawa T, Aoki S, Ren XQ,

et al. Reversal of the resistance to STI571 in human chronic

myelogenous leukemia K562 cells. Cancer Sci 2003;94557–63.

Nicolini FE, Hayette S, Corm S, Bachy E, Bories D, Tulliez M,

et al. Clinical outcome of 27 imatinib mesylate-resistant chronic

myelogenous leukemia patients harboring a T315I BCR-ABL

mutation. Haematologica 2007;92:1238–41.

Kumar L. Chronic myelogenous leukaemia (CML): An update.

Natl Med J India 2006;19:255–63.

Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics,

CA Cancer J Clin 2005;55:74–108.

Kingdom of Saudi Arabia, Ministry of Health, National Cancer

Registry. Cancer Incidence Report. 1999–2000. Available at:


Miller BA, Ries LAG, Hankey BF, Harras A, Edwards BK, (Eds).

SEER Cancer Statistics Review 1973–90. (NIH Pub No. 93-

. Bethesda MD: National Cancer Institute; 1993. p. 1–44.

Dieninger MW, O'Brien SG, Ford JM, Druker BJ. Practical

management of patients with chronic myeloid leukemia receiving

imatinib. J Clin Oncol 2003;21:1637–47.

Baccarani M, Dreyling M, ESMO Guidelines Working Group.

Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines

for diagnosis, treatment and follow-up. Ann Oncol 2010;(Suppl


Khalil SH, Abu-Amero KK, Al Mohareb F, Chaudhri NA.

Molecular monitoring of response to imatinib (Glivec) in chronic

myeloid leukemia patients: experience at a tertiary care hospital

in Saudi Arabia. Genet Test Mol Biomarkers 2010;14(1):67–74.

Aleem A, Siddiqui N. Chronic myeloid leukemia presenting with

extramedullary disease as massive ascites responding to imatinib

mesylate. Leuk Lymphoma 2005;46:1097–9.

Al-Qurashi F, Ayas M, Al Sharif F, Ibrahim E, Sahovic E, Al

Mahr M, Chaudhri N, et al. Second allogeneic bone marrow

transplantation after myeloablative conditioning analysis of 43

cases from single institution. Hematology 2004;9(2):123–9.

Gupta A, Prasad K. Hematological and Molecular Response

Evaluation of CML Patients on Imatinib. J Assoc Physicians

India 2007;55:109–13.

Mauro MJ. Defining and Managing Imatinib Resistance.

Hematology Am Soc Hematol Educ Program 2006;(1):219–25.

Hochhaus A, O’Brien SG, Guilhot F, Druker BJ, Branford S,

Foroni L, et al. Six-year follow-up of patients receiving imatinib

for the first-line treatment of chronic myeloid leukemia.

Leukemia 2009;23:1054–61.

Gambacorti-Passerin C, Antolini L, François-Xavier M, Guilhot

F, Deininger M, Fava C, et al. Multicenter Independent

J Ayub Med Coll Abbottabad 2012;24(2)


Assessment of Outcomes in Chronic Myeloid Leukemia Patients

Treated With Imatinib. J Natl Cancer Inst 2011;103:553–61.

Marley SB, Deininger MW, Davidson RJ, Goldman JM, Gordon

MY. The tyrosine kinase inhibitor STI571, like interferon-alpha,

preferentially reduces the capacity for amplification of

granulocyte-macrophage progenitors from patients with chronic

myeloid leukemia. Exp Hematol 2000;28(5):551–7.

Marley SB, Davidson RJ, Lewis JL, Nguyen DX, Eades A,

Parker S, et al. Progenitor cells from patients with advanced

phase chronic myeloid leukaemia respond to STI571 in vitro and

in vivo. Leuk Res 2001;25:997–1002.

Marley SB, Davidson RJ, Goldman JM, Gordon MY. Effects of

combinations of therapeutic agents on the proliferation of

progenitor cells in chronic myeloid leukaemia. Br J Haematol


Oetzel C, Jonuleit T, Gotz A, van der Kuip H, Michels H,

Duyster J, et al. The tyrosine kinase inhibitor CGP57148

(ST1571) induces apoptosis in BCR-ABL-positive cells by

down-regulating Bcl-X. Clin Cancer Res 2000;6:1958–68.

Gambacorti-Passerini C, le Coutre P, Mologni L, Fanelli M,

Bertazzoli C, Marchesi E et al. Inhibition of the ABL kinase

activity blocks the proliferation of BCR/ABL+ leukemic cells

and induces apoptosis. Blood Cells Mol Dis 1997;23: 380–94.

Alenzi FQ. Is there a link between apoptosis and chronic

leukemia. J Cell Sci Ther 2012;3:1–3.

Alenzi FQ, Wyse RK, Tamimi W, Bamaga M, Lotfy M. A close

link between Fas, p53 and Apaf-1 in chronic leukemia. Saudi

Med J 2007;28:1296–99.



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