Der Pathologe

, Volume 25, Issue 6, pp 428–436 | Cite as

Regression der Philadelphia-Chromosom (bcr/abl)-positiven Myelo- und Megakaryopoiese unter Imatinib(STI571)-Therapie bei chronischer myeloischer Leukämie (CML)

  • J. Thiele
  • H. M. Kvasnicka
  • E. Varus
  • S. Kriener
  • K. Engels
  • P. Staib
  • E. S. Ollig
  • M. Griesshammer
  • C. F. Waller
  • H. Pfeifer
  • A. Schmitt-Gräff
Schwerpunkt: Tumorregression—Originalarbeit

Zusammenfassung

Bei der CML kommt es nach Therapie mit Imatinib (STI571) zu auffallenden Veränderungen der Knochenmarkmorphologie. Bisher ist nicht bekannt, in welchem Ausmaß diese mit einem Verlust der bcr/abl-Translokation einhergehen. Um die therapiebedingte Regression der leukämischen Zellpopulation abzuklären, wurden 14 Patienten ausgewählt, die keinerlei Vorbehandlung aufwiesen.

Ein wesentlicher Therapieeffekt war eine Reduktion der CD61+-Megakaryozytenzahl. Die Mikroformen, die diese Erkrankung charakterisieren, wurden durch große, normal erscheinende Zellen ersetzt. Eine morphometrische Analyse bestätigte die signifikante Regression der atypischen Mikromegakaryozyten und erbrachte planimetrische Messwerte, die mit einer Normalisierung vereinbar waren. Eine Fluoreszenz-in-situ-Hybridisierung erfolgte bei 5 Patienten dieser Serie, die vor Therapiebeginn das bcr/abl-Gen in 70% aller myeloischen Zellen zeigten. Dabei ließ auch die Megakaryopoiese in etwa 65% der Mikromegakaryozyten entsprechende positive Signale erkennen. Nach Behandlung kam es zu einer deutlichen Reduzierung dieser bcr/abl+-Zellpopulationen, während die auftretenden großen Megakaryozyten kein entsprechendes Markergen hatten.

Da zytogenetisches Ansprechen und Reduktion der Mikromegakaryozyten miteinander gekoppelt sind, kann dieses als Merkmal zum Abschätzen des Therapieerfolges benutzt werden.

Schlüsselwörter

bcr/abl-Gen Megakaryozyten Imatinib Mesilat (Glivec) Leukämische Regression Knochenmarkbiopsien Chronische myeloische Leukämie 

Regression of the Philadelphia chromosome (bcr/abl)-positive myelo- and megakaryopoiesis after Imatinib (STI571) therapy in chronic myelogenous leukemia (CML)

Abstract

In chronic myeloid leukemia following therapy with Imatinib (STI571) hematologic and cytogenetic response is associated with conspicuous changes of bone marrow morphology. However, it is not known to which extent these alterations are accompanied by a loss of the bcr/abl translocation. To study regression of the leukemic cell population we recruited 14 patients lacking pretreatment. Therapy resulted in a reduction of CD61+ megakaryopoiesis. Dwarf megakaryocytes characteristic for this disorder were replaced by large, normally appearing cells of this lineage. Morphometric analysis confirmed the significant decrease in the number of micromegakaryocytes and yielded planimetric parameters in keeping with normalization. Moreover, a fluorescence in-situ hybridization study in five patients of this cohort revealed that before therapy 70% of all myeloid cells exhibited the bcr/abl gene. Regarding megakaryopoiesis about 65% of the micromegakaryocytes displayed positive signals. Following treatment these bcr/abl+ cell populations decreased significantly while the emerging large megakaryocytes lacked a proper labeling. Because cytogenetic response and reduction of atypical micromegakaryocytes are linked, this feature may be useful to monitor therapeutic efficacy.

Keywords

bcr/abl gene Megakaryocytes Imatinib mesylate (Gleevec) Leukemic regression Bone marrow biopsies Chronic myeloid leukemia 

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • J. Thiele
    • 1
    • 8
  • H. M. Kvasnicka
    • 1
  • E. Varus
    • 1
  • S. Kriener
    • 3
  • K. Engels
    • 3
  • P. Staib
    • 4
  • E. S. Ollig
    • 1
  • M. Griesshammer
    • 5
  • C. F. Waller
    • 6
  • H. Pfeifer
    • 7
  • A. Schmitt-Gräff
    • 2
  1. 1.Institut für PathologieUniversität Köln
  2. 2.Institut für PathologieUniversität Freiburg
  3. 3.Institut für PathologieUniversität Frankfurt
  4. 4.1. Medizinische KlinikUniversität Köln
  5. 5.3. Medizinische KlinikUniversität Ulm
  6. 6.Abteilung Hämatologie/OnkologieMedizinische Klinik, Universität Freiburg
  7. 7.Abteilung HämatologieZentrum Klinische Medizin, Universität Frankfurt
  8. 8.Zentrum für PathologieUniversität zu KölnKöln

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