FISH for BCR-ABL on interphases of peripheral blood neutrophils but not of unselected white cells correlates with bone marrow cytogenetics in CML patients treated with imatinib


Interphase fluorescence in situ hybridization (I-FISH) for the BCR-ABL translocation performed on peripheral blood (PB) white cells has been suggested as a surrogate for conventional bone marrow (BM) cytogenetics for monitoring patients with chronic myeloid leukemia (CML). I-FISH is faster, less costly, and does not require BM aspiration. For patients treated with interferon-alpha (IFN), a good correlation between the two methods has been demonstrated in several though not all studies. However, imatinib mesylate (STI571) has largely replaced IFN as the standard drug treatment for CML, raising the question if the results obtained in IFN-treated patients are applicable to patients on imatinib. We therefore compared the two methods in patients on imatinib and patients on other therapies, mainly IFN (collectively referred to as nonimatinib therapies). Our results demonstrate that the correlation between I-FISH and cytogenetics is much weaker in patients on imatinib than in patients on nonimatinib therapies. Correction of the I-FISH values for the proportion of lymphocytes barely improved the correlation, probably as a result of unpredictable proportions of Philadelphia-positive B cells. By contrast, I-FISH of PB neutrophils was much better correlated with BM cytogenetics. We conclude that I-FISH on unselected PB white cells is not suitable for monitoring patients on imatinib.


The molecular hallmark of chronic myeloid leukemia (CML) is the t(9;22)(q34;q11) (Philadelphia (Ph)) translocation, which is found in about 95% of all CML patients. As a result, a BCR-ABL fusion gene and protein are produced. The latter is a constitutively active tyrosine kinase that causes malignant transformation of a multipotent hemopoietic stem cell.1,2

Drug therapy of CML has traditionally relied on IFN as the only agent capable of producing long-term remissions, although only in a small subset of patients.3,4,5 The impressive rates of hematological and cytogenetic remissions seen with the Bcr-Abl-specific tyrosine kinase inhibitor imatinib have changed the therapeutic practice for patients who failed IFN.6,7 Based on vastly superior results in a randomized comparison with IFN/cytarabine, imatinib has now become the standard in newly diagnosed CML patients.8

The classical technique for diagnosis and follow-up of Ph-positive CML is G- or R-banding of BM metaphases. Disadvantages include high costs,9 the dependence on the growth of metaphases, and the fact that BM aspiration is an invasive and unpleasant procedure. Therefore, alternative methods like fluorescence in situ hybridization (FISH), reverse transcription-polymerase chain reaction (RT-PCR) or Southern blotting were evaluated as alternatives for monitoring.

Interphase FISH (I-FISH) to detect the BCR-ABL translocation in PB white cells has been compared to BM cytogenetics in a number of studies.10,11,12,13,14,15 Previous studies focused on patients treated with IFN-based drug therapy, allogeneic and autologous stem cell transplantation.10,13,16 While the correlation between I-FISH and BM metaphases is generally rather tight, there is considerable variation between studies, and there may be significant discrepancies between the two methods in individual patients. Most importantly, it is currently unknown if these results are applicable to patients on imatinib. In the present study, we compared I-FISH for BCR-ABL performed on PB leukocytes with BM cytogenetics in two cohorts of patients undergoing treatment with therapies other than imatinib and treatment with imatinib, respectively. Compared to patients on nonimatinib therapies, the correlation between PB FISH and BM cytogenetics was much weaker in patients on imatinib. Correction for lymphocytes (assessed by differential blood counts) did not significantly improve these results, while there was a much better correlation between BM cytogenetics and the Ph status of FACS-sorted PB neutrophils.

Materials and methods

Patients and samples (Table 1)

Table 1 Profiles of patients

Paired BM and PB specimens were studied in 15 CML patients on various therapies other than imatinib (interferon-alpha (IFN) based, 10; hydroxyurea, 1; autologous stem cell transplantation followed by IFN, 2; allogeneic stem cell transplantation, 2) and 15 patients treated with imatinib. In the latter patients, PB leukocytes were also FACS sorted into neutrophils, monocytes, B- and T cells. Informed consent according to the Declaration of Helsinki was obtained in all cases.


Mononuclear cells were isolated by Ficoll–Hypaque density-gradient centrifugation. Neutrophils were separated based on size and granularity. Specific antibodies were used to separate monocytes (CD14), B- (CD19) and T cells (CD3). Phycoerythrin (PE)-conjugated anti-CD14 (MΦP9-PE) and anti-CD19 (J4.119-PE) antibodies were from Beckman-Coulter (Fullerton, CA, USA). Fluorescein isothiocyanate (FITC)-conjugated anti-CD3 (SK7-FITC) was from Becton-Dickinson (Sunnyvale, CA, USA). Flow cytometry analysis and cell sorting were performed on a FACS Calibur (Becton Dickinson).

Preparation of cells for I-FISH

For prehybridization, PB specimens were incubated for 24 h in culture medium without cytokines (RPMI 1640, human AB serum, penicillin, streptomycin, L-glutamine). Next, colchicin was added, followed by another 3 h of incubation.

Preparation of cells for hypermetaphase FISH

BM aspirates were incubated for 24 h with colchicin in order to increase the number of metaphases for analysis.17

FISH hybridization

For detection of BCR-ABL, The LSI bcr-abl–DNA–ES probe (Vysis, Stuttgart, Germany) was used. Hybridization followed the manufacturer's protocol with slight modifications. FACS-sorted cells were immersed in 10 mM HCl/10% pepsin for 30 s at 37°C prior to hybridization. Signals were visualized under a Zeiss Axioskop microscope (Zeiss, Jena, Germany) using a FITC/Rhodamine dual band filter. A total of 25 metaphases or 500 interphase nuclei were analyzed in each sample if available. The cutoff for false-positive results is approximately 1% for unselected cells.18

Statistical analysis

All calculations were performed with the SPSS statistical package (SPSS GmbH, Munich, Germany). Categorical and noncategorical variables were compared by χ2 and Mann–Whitney U-test, respectively. Correlations were evaluated using Pearson's correlation coefficient.


The patient groups were comparable with respect to demographics and hematological parameters except that four patients in the imatinib group were in accelerated phase, whereas all other patients were in chronic phase (P<0. 05, Table 1). The median proportions of Ph-positive interphases in unselected PB white cells (43% with nonimatinib therapies, 40% with imatinib) and median Ph-positive BM metaphases (51 vs 52%) were also not different between the two groups.

Comparison between BM cytogenetics and I-FISH on unsorted PB white cells in patients treated with nonimatinib therapies

In all, 15 paired samples were available for analysis (Table 2). A median of 51.4% (range 0.6–100%) of BM metaphases and a median of 43.4% (range 0.5–82.7%) PB interphases were Ph positive. A strong correlation between the BM metaphases and PB interphases was observed (r=0.91, P<0.001, Figure 1a). However, there was a significant discordance in two patients (#3 and 9), where I-FISH detected a much lower proportion of BCR-ABL-positive cells.

Table 2 BM cytogenetics vs BCR-ABL status of PB in 15 CML patients on various nonimatinib therapies
Figure 1

Correlation between BM cytogenetics and BCR-ABL status of PB leukocytes. (a) Patients on conventional therapies and (b) patients on imatinib.

Comparison between BM cytogenetics and PB I-FISH in patients on imatinib

In analogy to the patients on nonimatinib therapies, we examined BM and PB white cells in 15 patients on imatinib.

Unsorted white cells

In total, 13 paired samples were examined with a median of Ph-positive metaphases of 52% (range 8–100%) in BM and a median of Ph-positive interphases of 40% (range 2–80.8%) in PB. The correlation between BM cytogenetics and PB leukocytes was much weaker than in patients on nonimatinib therapies (r=0.6428, P=0.013, Figure 1b), with major discrepancies observed in a number of cases (Table 3). In CML, most B-lymphocytes and almost all T-lymphocytes are reportedly Ph negative.19 In order to correct for this, the results obtained from PB were corrected by subtracting the percentage of lymphocytes as given by the differential counts from the same samples. This approach has been used in several studies in patients on nonimatinib treatment.12,20,21,22 However, the correction led only to a very moderate improvement of the correlation coefficient to 0.6817 (P=0.005).

Table 3 BM cytogenetics vs BCR-ABL status of white cell subpopulations in 15 CML patients treated with imatinib

Sorted cells

The weak correlation suggested that imatinib might preferentially eliminate certain subpopulations from the PB, while sparing others. We therefore separated the white blood cells from patients on imatinib according to their immunophenotype. False-positive cutoffs for FACS-sorted cells were established by analyzing 500 cells from each of five individuals with morphologically normal bone marrow. The false-positive cutoffs (mean+2 s.d.) were 0.2% for FACS-sorted neutrophils and T cells and 0.4% for monocytes and B cells. FACS-sorted cells from the 15 patients studied above were analyzed (Table 3).

The median Ph-positive BM metaphases were 40% (range 8–100%). In the PB, the median percentage of Ph-positive interphases was 35.2% (range 1.6–99.4%) in neutrophils, 24.8% (range 0–97.2%) in monocytes, 7.8% (range 0–38.2%) in B cells and 0.4% (range 0–7.4%) in T cells. As expected, there was no correlation between BM and PB for B cells (r=0.3772, P=0.15) and T cells (r=0.16, P=0.56). In contrast, there was a very good correlation between BM and PB neutrophils (r=0.89, P<0.001, Figure 2a), and reasonably good correlation between BM and PB monocytes (r=0.76, P=0.001, Figure 2b).

Figure 2

Correlation between BM cytogenetics and FACS-sorted PB cells. (a) Neutrophils and (b) monocytes in patients on imatinib.


Several diagnostic methods are available to detect the BCR-ABL rearrangement at different biological levels. Conventional cytogenetics has been the gold standard for decades and is well validated in patients on IFN.3,4,23 Limitations of conventional karyotyping include its high costs, a considerable rate of failure due to lack of metaphases, and the need for bone marrow aspiration, an invasive and painful procedure. Detection of BCR-ABL in PB leukocytes by I-FISH has therefore been proposed as an alternative to conventional cytogenetics. In most direct comparisons, the two methods showed a good correlation, however, with considerable differences between individual studies.10,11,12,13,15,16 For example, Le Gouill et al observed an extremely good correlation (r=0.97) between I-FISH of PB and BM cytogenetics, while Lesser et al found a significant but considerably weaker correlation (r=0.78). In addition, individual cases may exhibit significant discrepancies.15,24 These discrepancies may be related not only to the analysis of interphase vs metaphase cells but also to the fact that in some patients, the proportion of clonogenic Ph-negative cells is higher in the PB than the BM.25 Our data show a good correlation between BM metaphases and PB interphases in unselected white blood cells, with a correlation coefficient of 0.91, exactly as recently reported by Schoch et al.13 Nonetheless, there were large discrepancies in some patients (#3 and 9, Table 2). Generally, PB IP-FISH results tended to be lower than BM metaphases, in accordance with other reports.13,15 This indicates that I-FISH may lead to a bias toward better responses.

In contrast, the correlation found in imatinib-treated patients, although significant, was much weaker (r=0.64, P=0.013), rendering I-FISH of total white blood cells of little use for the follow-up of individual patients. It has been proposed that the results of PB I-FISH should be corrected by subtraction of the lymphocytes, which are not usually part of the leukemic clone. However, correction for the lymphocytes (as assessed by standard differential blood count) only marginally improved the correlation coefficient. However, this shortcoming could be overcome by analyzing FACS-sorted PB neutrophils, for which again a good correlation with BM cytogenetics was found (r=0.89, P<0.001). Importantly, in our study, neutrophils were selected by flow cytometry based on their size and forward scatter distribution only, without the use of specific antibodies. Such separation is fast, inexpensive and thus useful for routine clinical applications in accordingly equipped laboratories. However, there were still significant discrepancies between the BM and PB neutrophils in several patients on imatinib (#7, 10, 13, Table 3). It has been suggested that BCR-ABL-negative neutrophils are preferentially released into the PB in some patients,24 but it remains unclear why this occurs in some patients while sparing others. Analysis of a larger cohort of patients will be necessary to determine the exact incidence of such large discrepancies.

A weaker correlation was also found for monocytes (r=0.76), making them a less suitable choice for clinical applications; moreover, their separation by FACS sorting with the use of antibodies is much more laborious and expensive than those of neutrophils. In keeping with published data,19,26,27 PB B cells were largely, and T cells almost exclusively Ph negative. However, there were large variations between individual patients with respect to the Ph status of B cells (Table 2). Thus, B cells may contribute to the Ph-positive cells in the PB in an unpredictable manner, which partially explains the large variations among individual patients. The apparent difference between patients on imatinib and patients on other therapies (mainly IFN) suggests that both agents may have a differential effect on the various populations of white cells. Unfortunately, it is no longer possible to test this, since most patients on IFN, unless in complete cytogenetic response, have been switched to imatinib.

Quantitative RT-PCR (Q-PCR) for the detection of BCR-ABL transcripts has emerged as yet another alternative to BM cytogenetics. Q-PCR is of established value in monitoring patients in complete cytogenetic response after allogeneic BMT28 or on IFN therapy,29 and is also widely used to follow patients on imatinib,30,31,32,33 where it may aid prognostication. A recent comparison found a tight correlation between Q-PCR, hypermetaphase FISH, I-FISH and conventional cytogenetics in the BM.13 However, the results await confirmation in controlled trials with survival or progression-free survival as end points.

Both Q-PCR and I-FISH measure static parameters, the percentage of cells with a BCR-ABL rearrangement and the average steady-state level of BCR-ABL mRNA, respectively. By contrast, metaphase karyotyping incorporates a functional test, namely the capacity of cells to proliferate in defined conditions, and this may aid its prognostic power. Achievement of a major cytogenetic response at 3 months predicts progression-free survival in patients treated with imatinib in chronic and accelerated phase.6,34 In addition, only conventional cytogenetics is capable of detecting additional chromosomal abnormalities in Ph-positive or Ph-negative cells. In the former cells, this appears to indicate disease progression;35 in the latter cells, it may be associated with a myelodysplastic syndrome.36 In both scenarios, conventional karyotyping provides vital information.

In summary, I-FISH of unselected white blood cells is not useful for monitoring of patients on imatinib. Analysis of neutrophils seems to improve the results and may be useful if a FACS sorter is available. It is likely that in the future, the various diagnostic tests will be used complementarily. Until validation in controlled trials with clinical end points is available, conventional karyotyping should remain the mainstay for monitoring CML patients.


  1. 1

    Deininger MW, Goldman JM, Melo JV . The molecular biology of chronic myeloid leukemia. Blood 2000; 96: 3343–3356.

  2. 2

    Sawyers CL . Chronic myeloid leukemia. N Engl J Med 1999; 340: 1330–1340.

  3. 3

    Talpaz M, Kantarjian H, Kurzrock R, Trujillo JM, Gutterman JU . Interferon-alpha produces sustained cytogenetic responses in chronic myelogenous leukemia. Philadelphia chromosome-positive patients. Ann Intern Med 1991; 114: 532–538.

  4. 4

    The Italian Cooperative Study Group on Chronic Myeloid Leukemia. Long-term follow-up of the Italian trial of interferon-alpha versus conventional chemotherapy in chronic myeloid leukemia. Blood 1998; 92: 1541–1548.

  5. 5

    Hehlmann R, Heimpel H, Hossfeld DK, Hasford J, Kolb HJ, Loffler H et al. Randomized study of the combination of hydroxyurea and interferon alpha versus hydroxyurea monotherapy during the chronic phase of chronic myelogenous leukemia (CML Study II). The German CML Study Group. Bone Marrow Transplant 1996; 17 (Suppl. 3): S21–S24.

  6. 6

    Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schiffer C, Gambacorti-Passerini C et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 2002; 346: 645–652.

  7. 7

    Kantarjian HM, Talpaz M, O'Brien S, Smith TL, Giles FJ, Faderl S et al. Imatinib mesylate for Philadelphia chromosome-positive, chronic-phase myeloid leukemia after failure of interferon-alpha: follow-up results. Clin Cancer Res 2002; 8: 2177–2187.

  8. 8

    O'Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2003; 348: 994–1004.

  9. 9

    Tbakhi A, Pettay J, Sreenan JJ, Abdel-Razeq H, Kalaycio M, Hoeltge G et al. Comparative analysis of interphase FISH and RT-PCR to detect bcr-abl translocation in chronic myelogenous leukemia and related disorders. Am J Clin Pathol 1998; 109: 16–23.

  10. 10

    Seong D, Thall P, Kantarjian HM, Talpaz M, Swantkowski J, Xu J et al. Philadelphia chromosome-positive myeloid cells in the peripheral blood of chronic myelogenous leukemia patients: comparison with the frequency detected in cycling cells of the bone marrow. Clin Cancer Res 1998; 4: 861–867.

  11. 11

    Yanagi M, Shinjo K, Takeshita A, Tobita T, Yano K, Kobayashi M et al. Simple and reliably sensitive diagnosis and monitoring of Philadelphia chromosome-positive cells in chronic myeloid leukemia by interphase fluorescence in situ hybridization of peripheral blood cells. Leukemia 1999; 13: 542–552.

  12. 12

    Muhlmann J, Thaler J, Hilbe W, Bechter O, Erdel M, Utermann G et al. Fluorescence in situ hybridization (FISH) on peripheral blood smears for monitoring Philadelphia chromosome-positive chronic myeloid leukemia (CML) during interferon treatment: a new strategy for remission assessment. Genes Chromosomes Cancer 1998; 21: 90–100.

  13. 13

    Schoch C, Schnittger S, Bursch S, Gerstner D, Hochhaus A, Berger U et al. Comparison of chromosome banding analysis, interphase- and hypermetaphase-FISH, qualitative and quantitative PCR for diagnosis and for follow-up in chronic myeloid leukemia: a study on 350 cases. Leukemia 2002; 16: 53–59.

  14. 14

    Faderl S, Kantarjian HM, Talpaz M, O'Brien S . New treatment approaches for chronic myelogenous leukemia. Semin Oncol 2000; 27: 578–586.

  15. 15

    Lesser ML, Dewald GW, Sison CP, Silver RT . Correlation of three methods of measuring cytogenetic response in chronic myelocytic leukemia. Cancer Genet Cytogenet 2002; 137: 79–84.

  16. 16

    Le Gouill S, Talmant P, Milpied N, Daviet A, Ancelot M, Moreau P et al. Fluorescence in situ hybridization on peripheral-blood specimens is a reliable method to evaluate cytogenetic response in chronic myeloid leukemia. J Clin Oncol 2000; 18: 1533–1538.

  17. 17

    Seong D, Kantarjian HM, Albitar M, Arlinghaus R, Xu J, Talpaz M et al. Analysis of Philadelphia chromosome-negative BCR-ABL-positive chronic myelogenous leukemia by hypermetaphase fluorescence in situ hybridization. Ann Oncol 1999; 10: 955–959.

  18. 18

    Deininger M, Lehmann T, Krahl R, Hennig E, Muller C, Niederwieser D . No evidence for persistence of BCR-ABL-positive cells in patients in molecular remission after conventional allogenic transplantation for chronic myeloid leukemia. Blood 2000; 96: 779–780.

  19. 19

    Takahashi N, Miura I, Saitoh K, Miura AB . Lineage involvement of stem cells bearing the Philadelphia chromosome in chronic myeloid leukemia in the chronic phase as shown by a combination of fluorescence-activated cell sorting and fluorescence in situ hybridization. Blood 1998; 92: 4758–4763.

  20. 20

    Froncillo MC, Maffei L, Cantonetti M, Del Poeta G, Lentini R, Bruno A et al. FISH analysis for CML monitoring? Ann Hematol 1996; 73: 113–119.

  21. 21

    Cox-Froncillo MC, Cantonetti M, Masi M, Lentini R, Giudiceandrea P, Maffei L et al. Cytogenetic analysis is non-informative for assessing the remission rate in chronic myeloid leukemia (CML) patients on interferon-alpha (IFN-alpha) therapy. Cancer Genet Cytogenet 1995; 84: 15–18.

  22. 22

    Nolte M, Werner M, Ewig M, von Wasielewski R, Wilkens L, Link H et al. Fluorescence in situ hybridization (FISH) is a reliable diagnostic tool for detection of the 9;22 translocation. Leukemia Lymphoma 1996; 22: 287–294.

  23. 23

    Hehlmann R, Heimpel H, Hasford J, Kolb HJ, Pralle H, Hossfeld DK et al. Randomized comparison of interferon-alpha with busulfan and hydroxyurea in chronic myelogenous leukemia. The German CML Study Group. Blood 1994; 84: 4064–4077.

  24. 24

    Sinclair PB, Green AR, Grace C, Nacheva EP . Improved sensitivity of BCR-ABL detection: a triple-probe three-color fluorescence in situ hybridization system. Blood 1997; 90: 1395–1402.

  25. 25

    Sick C, Schultheis B, Pasternak G, Kottke I, Horner S, Heissig B et al. Predominantly BCR-ABL negative myeloid precursors in interferon-alpha treated chronic myelogenous leukemia: a follow-up study of peripheral blood colony-forming cells with fluorescence in situ hybridization. Ann Hematol 2001; 80: 9–16.

  26. 26

    Garicochea B, Chase A, Lazaridou A, Goldman JM . T lymphocytes in chronic myelogenous leukaemia (CML): no evidence of the BCR/ABL fusion gene detected by fluorescence in situ hybridization in 14 patients. Leukemia 1994; 8: 1197–1201.

  27. 27

    Eibl B, Ebner S, Duba C, Bock G, Romani N, Erdel M et al. Dendritic cells generated from blood precursors of chronic myelogenous leukemia patients carry the Philadelphia translocation and can induce a CML-specific primary cytotoxic T-cell response. Genes Chromosomes Cancer 1997; 20: 215–223.

  28. 28

    Cross NC, Feng L, Chase A, Bungey J, Hughes TP, Goldman JM . Competitive polymerase chain reaction to estimate the number of BCR-ABL transcripts in chronic myeloid leukemia patients after bone marrow transplantation. Blood 1993; 82: 1929–1936.

  29. 29

    Hochhaus A, Lin F, Reiter A, Skladny H, Mason PJ, van Rhee F et al. Quantification of residual disease in chronic myelogenous leukemia patients on interferon-alpha therapy by competitive polymerase chain reaction. Blood 1996; 87: 1549–1555.

  30. 30

    Merx K, Muller MC, Kreil S, Lahaye T, Paschka P, Schoch C et al. Early reduction of BCR-ABL mRNA transcript levels predicts cytogenetic response in chronic phase CML patients treated with imatinib after failure of interferon alpha. Leukemia 2002; 16: 1579–1583.

  31. 31

    Wang L, Pearson K, Pillitteri L, Ferguson JE, Clark RE . Serial monitoring of BCR-ABL by peripheral blood real-time polymerase chain reaction predicts the marrow cytogenetic response to imatinib mesylate in chronic myeloid leukaemia. Br J Haematol 2002; 118: 771–777.

  32. 32

    Wang L, Pearson K, Ferguson JE, Clark RE . The early molecular response to imatinib predicts cytogenetic and clinical outcome in chronic myeloid leukaemia. Br J Haematol 2003; 120: 990–999.

  33. 33

    Kantarjian HM, Talpaz M, Cortes J, O'Brien S, Faderl S, Thomas D et al. Quantitative polymerase chain reaction monitoring of BCR-ABL during therapy with imatinib mesylate (STI571; Gleevec) in chronic-phase chronic myelogenous leukemia. Clin Cancer Res 2003; 9: 160–166.

  34. 34

    Talpaz M, Silver RT, Druker BJ, Goldman JM, Gambacorti-Passerini C, Guilhot F et al. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood 2002; 99: 1928–1937.

  35. 35

    Marin D, Marktel S, Bua M, Armstrong L, Goldman JM, Apperley JF et al. The use of imatinib (STI571) in chronic myelod leukemia: some practical considerations. Haematologica 2002; 87: 979–988.

  36. 36

    Bumm T, Muller C, Al Ali HK, Krohn K, Shepherd P, Schmidt E et al. Emergence of clonal cytogenetic abnormalities in Ph-cells in some CML patients in cytogenetic remission to imatinib but restoration of polyclonal hematopoiesis in the majority. Blood 2003; 101: 1941–1949.

Download references


We thank Dr Haifa-Kathrin Al-Ali for dedicated patient care. We are grateful to Ms Christel Müller, Ms Christina Franke and Ms Daniela Klug for excellent technical assistance.

Author information

Correspondence to M W N Deininger.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Reinhold, U., Hennig, E., Leiblein, S. et al. FISH for BCR-ABL on interphases of peripheral blood neutrophils but not of unselected white cells correlates with bone marrow cytogenetics in CML patients treated with imatinib. Leukemia 17, 1925–1929 (2003).

Download citation


  • CML
  • imatinib
  • FISH

Further reading