Myelodysplastic syndrome, MDS

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• Myelodysplastic syndrome, MDS

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MDS

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  ???,????????????????????,?????????????????

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• ?????(preleukemic disorder)

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2. ???????

• - ?????/???????????
• - ???????????????

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Known molecular abnormalities in MDS
Gene Type of anomaly Incidence ()
RAS Point mutation (codon 12, 13 or 61) 10-30
P53 Point mutation or deletion of other allele 5
FMS (encodes M-CSF receptor) Point mutation (codon 969 or rarely 301) 5-10
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• ??p53, FLT3(fam??????3), RAS??
• ???????????? (e.g. -5, -7, etc.)

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3.????

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4. ??

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???MDS

• ??????????(JMML)
• ?? 7 ?????????
• ??? MDS
• ??? MDS
• Refractory Anemia
• Refractory Anemia with Ring Sideroblasts (RARS)
• Refractory Anemia with Excess Blasts (RAEB)
• RAEB in Transformation (RAEB-t)
• CMML

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???MDS

• ??? MDS
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• ???MDS
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• ????AA

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??????? 85 ????,???,?????(???), MOPP,
???? ??????? 5-7 ? ????????? 15
VP-16,????,???? ?????? 2 ? Both rapidly
progressive to AML - poor prognosis
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5. ????

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• 2. ??? ??? ??
• 3. ????ALIP??
• 4. ?????CFU-GM,CFU-E,BFU-E
• 5. ??????????????
• 6. ????
• 7. ?? ???
• 8. ??????????? ???

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• ???????????????????????????,??????????????????????
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• ?????????,MCV?gt95fl??????????,???????,????????????
  ?????????????(??gt??????2?)
• ??????????

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• ????????lt2109/L,??????
• ??????????????????????(??Pelger-Huët??)????????90
  ????,????????????????
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• ???????1/2-2/3??,?????????,??????????????
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• 50??????????????(ALIP),??????????????????????(5-8
  ???)?????????
• ???????????????????????,??ALIP?????
• ??

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• ?????(CFU-mix)????????,??MDS???????????
• CFU-GM CFU-E,BFU-E
• RA,RAS ??/?? ??/??
• RAEB ?? ??
• RAEBt ?? ??
• CMMOL ?? ??
• ??

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• MDS?????????????4070
• ????????8,20q-, -5/5q-, -7/7q-
• MDS???????????????????
• RAEB???????????,?????????
• 
  ??

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MDS - Dysplastic Erythroblasts
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??????? (dyserythropoiesis)
Normal
Dyserythropoiesis
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Howell-Jolly??
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MDS-RARS(???)
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Ringed sideroblasts
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MDS-RAEB
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MDS-CMMOL
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MDS-RAEBt
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MDS-RAEBt(?????) ??
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• ??????PNH??????
• HbF??
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• ???????
• 
  ??

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FAB Classification
Ringed Sideroblasts PB Blasts BM Blasts PB Monocytes
RA lt 1 lt 5
RARS gt 15 lt 1 lt 5
RAEB lt 5 5-20
RAEB-T gt 5 21-30
CMML lt 5 20 gt 1 X 109 /L
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WHO Classification System

• Myelodysplastic Syndromes(MDS)
• Refractory Anemia (RA)
• With ringed sideroblasts (RARS)
• Without ringed siderblasts
• Refractory Cytopenia (MDS) with Multilineage
  Dysplasia (RCMD)
• Refractory Anemia with Excess Blasts (RAEB)
• 5q- syndrome
• Myelodysplastic syndrome, unclassifiable

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WHO Classification System

• Myelodysplastic/Myeloproliferative Diseases
• Chronic Myelomonocytic Leukemia (CMML)
• Atypical Chronic Myelogenous Leukemia (aCML)
• Leukemia (???????????JMML)

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?????????

• AA AML
• MDS AL ALL
• PNH ???
• MPD

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??(Prognosis)

• longest median survival for RARS and RA(????gt5?)
• worst for RAEB and RAEB-T(?lt1?)
• increased risk of developing AML, especially for
  RAEB-T
• 50????????????????????
• ???????AML?????????

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Cytogenetics and prognosis

• Good risk
• Normal, isolated 5q-, isolated 20q-, -Y
• Poor risk
• Complex changes (gt 3 abnormalities)
• Chromosome 7 abnormalities
• Intermediate risk
• All other changes

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• ??MDS?
• ??MDS????????????
• ??MDS?AL?AA?MPD??????